- Asrani, S. K., Devarbhavi, H., Eaton, J. & Kamath, P. S. Burden of liver diseases in the world. J. Hepatol. 70, 151–171 (2019).
PubMed Google Scholar
- Paik, J. M., Golabi, P., Younossi, Y., Mishra, A., Younossi, Z. M. Changes in the global burden of chronic liver diseases from 2012 to 2017: the growing impact of nonalcoholic fatty liver disease. Hepatology (2020). in press, https://doi.org/10.1002/hep.31173.
- Crabb, D. W., Im, G. Y., Szabo, G., Mellinger, J. L. & Lucey, M. R. Diagnosis and treatment of alcohol-associated liver diseases: 2019 practice guidance from the American Association for the Study of Liver Diseases. Hepatology 71, 306–333 (2020).
PubMed Google Scholar
- Friedman, S. L., Neuschwander-Tetri, B. A., Rinella, M. & Sanyal, A. J. Mechanisms of NAFLD development and therapeutic strategies. Nat. Med. 24, 908–922 (2018).
CAS PubMed PubMed Central Google Scholar
- Liaskou, E., Hirschfield, G. M. & Gershwin, M. E. Mechanisms of tissue injury in autoimmune liver diseases. Semin. Immunopathol. 36, 553–568 (2014).
CAS PubMed Google Scholar
- Gao, B., Ahmad, M. F., Nagy, L. E. & Tsukamoto, H. Inflammatory pathways in alcoholic steatohepatitis. J. Hepatol. 70, 249–259 (2019).
PubMed PubMed Central Google Scholar
- Koyama, Y. & Brenner, D. A. Liver inflammation and fibrosis. J. Clin. Investig. 127, 55–64 (2017).
PubMed Google Scholar
- Wree, A., Holtmann, T. M., Inzaugarat, M. E. & Feldstein, A. E. Novel drivers of the inflammatory response in liver injury and fibrosis. Semin. Liver Dis. 39, 275–282 (2019).
CAS PubMed Google Scholar
- Radaeva, S. et al. Interferon-alpha activates multiple STAT signals and down-regulates c-Met in primary human hepatocytes. Gastroenterology 122, 1020–1034 (2002).
CAS PubMed Google Scholar
- Hermant, P. et al. Human but not mouse hepatocytes respond to interferon-lambda in vivo. PLoS ONE 9, e87906 (2014).
PubMed PubMed Central Google Scholar
- Koestner, W. et al. Interferon-beta expression and type I interferon receptor signaling of hepatocytes prevent hepatic necrosis and virus dissemination in Coxsackievirus B3-infected mice. PLoS Pathog. 14, e1007235 (2018).
PubMed PubMed Central Google Scholar
- Lercher, A. et al. Type I interferon signaling disrupts the hepatic urea cycle and alters systemic metabolism to suppress T cell function. Immunity 51, 1074–1087 e9 (2019).
CAS PubMed PubMed Central Google Scholar
- Eslam, M., Ahlenstiel, G. & George, J. Interferon lambda and liver fibrosis. J. Interferon Cytokine Res. 39, 627–635 (2019).
CAS PubMed Google Scholar
- Eslam, M. et al. Interferon-lambda rs12979860 genotype and liver fibrosis in viral and non-viral chronic liver disease. Nat. Commun. 6, 6422 (2015).
CAS PubMed PubMed Central Google Scholar
- Wei, J. et al. SNX8 mediates IFNgamma-triggered noncanonical signaling pathway and host defense against Listeria monocytogenes. Proc. Natl Acad. Sci. USA 114, 13000–13005 (2017).
CAS PubMed Google Scholar
- Dunn, G. P., Koebel, C. M. & Schreiber, R. D. Interferons, immunity and cancer immunoediting. Nat. Rev. Immunol. 6, 836–848 (2006).
CAS PubMed Google Scholar
- Chen, Y., Hao, X., Sun, R., Wei, H. & Tian, Z. Natural killer cell-derived interferon-gamma promotes hepatocellular carcinoma through the epithelial cell adhesion molecule-epithelial-to-mesenchymal transition axis in hepatitis B virus transgenic mice. Hepatology 69, 1735–1750 (2019).
CAS PubMed Google Scholar
- Kalathil, S. G., Hutson, A., Barbi, J., Iyer, R. & Thanavala, Y. Augmentation of IFN-gamma+ CD8+ T cell responses correlates with survival of HCC patients on sorafenib therapy. JCI Insight 4, e130116 (2019).
PubMed Central Google Scholar
- Zeng, Z. et al. Interferon-gamma facilitates hepatic antiviral T cell retention for the maintenance of liver-induced systemic tolerance. J. Exp. Med. 213, 1079–1093 (2016).
CAS PubMed PubMed Central Google Scholar
- Wang, H. et al. TNF-alpha/IFN-gamma profile of HBV-specific CD4 T cells is associated with liver damage and viral clearance in chronic HBV infection. J. Hepatol. 72, 45–56 (2020).
CAS PubMed Google Scholar
- Bae, H. R. et al. Chronic expression of interferon-gamma leads to murine autoimmune cholangitis with a female predominance. Hepatology 64, 1189–1201 (2016).
CAS PubMed PubMed Central Google Scholar
- Ravichandran, G. et al. Interferon-gamma-dependent immune responses contribute to the pathogenesis of sclerosing cholangitis in mice. J. Hepatol. 71, 773–782 (2019).
CAS PubMed Google Scholar
- Glaser, F. et al. Liver infiltrating T cells regulate bile acid metabolism in experimental cholangitis. J. Hepatol. 71, 783–792 (2019).
CAS PubMed Google Scholar
- Radaeva, S. et al. Natural killer cells ameliorate liver fibrosis by killing activated stellate cells in NKG2D-dependent and tumor necrosis factor-related apoptosis-inducing ligand-dependent manners. Gastroenterology 130, 435–452 (2006).
CAS PubMed Google Scholar
- Jeong, W. I., Park, O., Radaeva, S. & Gao, B. STAT1 inhibits liver fibrosis in mice by inhibiting stellate cell proliferation and stimulating NK cell cytotoxicity. Hepatology 44, 1441–1451 (2006).
CAS PubMed Google Scholar
- Weng, H., Mertens, P. R., Gressner, A. M. & Dooley, S. IFN-gamma abrogates profibrogenic TGF-beta signaling in liver by targeting expression of inhibitory and receptor Smads. J. Hepatol. 46, 295–303 (2007).
CAS PubMed Google Scholar
- Gao, B. Cytokines, STATs and liver disease. Cell Mol. Immunol. 2, 92–100 (2005).
CAS PubMed Google Scholar
- He, X. et al. MicroRNA-351 promotes schistosomiasis-induced hepatic fibrosis by targeting the vitamin D receptor. Proc. Natl Acad. Sci. USA 115, 180–185 (2018).
CAS PubMed Google Scholar
- Tosello-Trampont, A. C. et al. NKp46(+) natural killer cells attenuate metabolism-induced hepatic fibrosis by regulating macrophage activation in mice. Hepatology 63, 799–812 (2016).
CAS PubMed PubMed Central Google Scholar
- Hart, K. M. et al. Type 2 immunity is protective in metabolic disease but exacerbates NAFLD collaboratively with TGF-beta. Sci. Transl. Med. 9, eaal3694 (2017).
PubMed Google Scholar
- Xiang, X. et al. Interleukin-22 ameliorates acute-on-chronic liver failure by reprogramming impaired regeneration pathways in mice. J. Hepatol. 72, 736–745 (2020).
CAS PubMed Google Scholar
- Wallach, D. et al. Tumor necrosis factor receptor and Fas signaling mechanisms. Annu. Rev. Immunol. 17, 331–367 (1999).
CAS PubMed Google Scholar
- Boetticher, N. C. et al. A randomized, double-blinded, placebo-controlled multicenter trial of etanercept in the treatment of alcoholic hepatitis. Gastroenterology 135, 1953–1960 (2008).
CAS PubMed PubMed Central Google Scholar
- Su, L. et al. Kupffer cell-derived TNF-alpha promotes hepatocytes to produce CXCL1 and mobilize neutrophils in response to necrotic cells. Cell Death Dis. 9, 323 (2018).
PubMed PubMed Central Google Scholar
- Hwang, S. et al. Protective and detrimental roles of p38alpha MAPK in different stages of nonalcoholic fatty liver disease. Hepatology 72, 873–891 (2020).
- Hwang, S. et al. Interleukin-22 ameliorates neutrophil-driven nonalcoholic steatohepatitis through multiple targets. Hepatology 72, 412–429 (2019).
Google Scholar
- Choi, Y. S. et al. Tumor necrosis factor-producing T-regulatory cells are associated with severe liver injury in patients with acute hepatitis A. Gastroenterology 154, 1047–1060 (2018).
CAS PubMed Google Scholar
- Li, X. F. et al. Chronic inflammation-elicited liver progenitor cell conversion to liver cancer stem cell with clinical significance. Hepatology 66, 1934–1951 (2017).
CAS PubMed Google Scholar
- Tan, W. et al. TNF-alpha is a potential therapeutic target to overcome sorafenib resistance in hepatocellular carcinoma. EBioMedicine 40, 446–456 (2019).
PubMed Google Scholar
- Tait Wojno, E. D., Hunter, C. A. & Stumhofer, J. S. The immunobiology of the interleukin-12 family: room for discovery. Immunity 50, 851–870 (2019).
CAS PubMed Google Scholar
- Hou, X. et al. CD205-TLR9-IL-12 axis contributes to CpG-induced oversensitive liver injury in HBsAg transgenic mice by promoting the interaction of NKT cells with Kupffer cells. Cell Mol. Immunol. 14, 675–684 (2017).
CAS PubMed Google Scholar
- Dias, J. et al. Chronic hepatitis delta virus infection leads to functional impairment and severe loss of MAIT cells. J. Hepatol. 71, 301–312 (2019).
CAS PubMed PubMed Central Google Scholar
- Heymann, F. & Tacke, F. Immunology in the liver-from homeostasis to disease. Nat. Rev. Gastroenterol. Hepatol. 13, 88–110 (2016).
CAS PubMed Google Scholar
- Everts, B. et al. Migratory CD103+ dendritic cells suppress helminth-driven type 2 immunity through constitutive expression of IL-12. J. Exp. Med. 213, 35–51 (2016).
CAS PubMed PubMed Central Google Scholar
- Liberal, R. et al. Regulatory T-cell conditioning endows activated effector T cells with suppressor function in autoimmune hepatitis/autoimmune sclerosing cholangitis. Hepatology 66, 1570–1584 (2017).
CAS PubMed PubMed Central Google Scholar
- Schwinge, D. et al. Dysfunction of hepatic regulatory T cells in experimental sclerosing cholangitis is related to IL-12 signaling. J. Hepatol. 66, 798–805 (2017).
CAS PubMed Google Scholar
- Busato, D. et al. Novel immunotherapeutic approaches for hepatocellular carcinoma treatment. Expert Rev. Clin. Pharmacol. 12, 453–470 (2019).
CAS PubMed Google Scholar
- Liu, Y. et al. Armored inducible expression of IL-12 enhances antitumor activity of glypican-3-targeted chimeric antigen receptor-engineered T cells in hepatocellular carcinoma. J. Immunol. 203, 198–207 (2019).
CAS PubMed Google Scholar
- Malek, T. R. The biology of interleukin-2. Annu. Rev. Immunol. 26, 453–479 (2008).
CAS PubMed Google Scholar
- Tan, X. et al. Elevated hepatic CD1d levels coincide with invariant NKT cell defects in chronic hepatitis B virus infection. J. Immunol. 200, 3530–3538 (2018).
CAS PubMed Google Scholar
- Salimzadeh, L. et al. PD-1 blockade partially recovers dysfunctional virus-specific B cells in chronic hepatitis B infection. J. Clin. Investig. 128, 4573–4587 (2018).
PubMed Google Scholar
- Pallett, L. J. et al. IL-2(high) tissue-resident T cells in the human liver: sentinels for hepatotropic infection. J. Exp. Med. 214, 1567–1580 (2017).
CAS PubMed PubMed Central Google Scholar
- Wing, K. & Sakaguchi, S. Regulatory T cells exert checks and balances on self tolerance and autoimmunity. Nat. Immunol. 11, 7–13 (2010).
CAS PubMed Google Scholar
- Klatzmann, D. & Abbas, A. K. The promise of low-dose interleukin-2 therapy for autoimmune and inflammatory diseases. Nat. Rev. Immunol. 15, 283–294 (2015).
CAS PubMed Google Scholar
- Liberal, R. et al. In autoimmune hepatitis type 1 or the autoimmune hepatitis-sclerosing cholangitis variant defective regulatory T-cell responsiveness to IL-2 results in low IL-10 production and impaired suppression. Hepatology 62, 863–875 (2015).
CAS PubMed Google Scholar
- Taubert, R. et al. Intrahepatic regulatory T cells in autoimmune hepatitis are associated with treatment response and depleted with current therapies. J. Hepatol. 61, 1106–1114 (2014).
CAS PubMed Google Scholar
- Jeffery, H. C. et al. Low-dose interleukin-2 promotes STAT-5 phosphorylation, Treg survival and CTLA-4-dependent function in autoimmune liver diseases. Clin. Exp. Immunol. 188, 394–411 (2017).
CAS PubMed PubMed Central Google Scholar
- Taylor, A. E. et al. Interleukin 2 promotes hepatic regulatory T cell responses and protects from biliary fibrosis in murine sclerosing cholangitis. Hepatology 68, 1905–1921 (2018).
CAS PubMed PubMed Central Google Scholar
- Gu, J. et al. Human CD39(hi) regulatory T cells present stronger stability and function under inflammatory conditions. Cell Mol. Immunol. 14, 521–528 (2017).
CAS PubMed Google Scholar
- Wills-Karp, M. et al. Interleukin-13: central mediator of allergic asthma. Science 282, 2258–2261 (1998).
CAS PubMed Google Scholar
- Grunig, G. et al. Requirement for IL-13 independently of IL-4 in experimental asthma. Science 282, 2261–2263 (1998).
CAS PubMed PubMed Central Google Scholar
- Bao, K. & Reinhardt, R. L. The differential expression of IL-4 and IL-13 and its impact on type-2 immunity. Cytokine 75, 25–37 (2015).
CAS PubMed PubMed Central Google Scholar
- McCormick, S. M. & Heller, N. M. Commentary: IL-4 and IL-13 receptors and signaling. Cytokine 75, 38–50 (2015).
CAS PubMed PubMed Central Google Scholar
- Ouyang, W. et al. Stat6-independent GATA-3 autoactivation directs IL-4-independent Th2 development and commitment. Immunity 12, 27–37 (2000).
CAS PubMed Google Scholar
- Ramsay, N. K. & Kersey, J. H. Indications for marrow transplantation in acute lymphoblastic leukemia. Blood 75, 815–818 (1990).
CAS PubMed Google Scholar
- Zheng, T. et al. IL-13 receptor alpha2 selectively inhibits IL-13-induced responses in the murine lung. J. Immunol. 180, 522–529 (2008).
CAS PubMed Google Scholar
- Fichtner-Feigl, S., Strober, W., Kawakami, K., Puri, R. K. & Kitani, A. IL-13 signaling through the IL-13alpha2 receptor is involved in induction of TGF-beta1 production and fibrosis. Nat. Med. 12, 99–106 (2006).
CAS PubMed Google Scholar
- Gieseck, R. L. 3rd, Wilson, M. S. & Wynn, T. A. Type 2 immunity in tissue repair and fibrosis. Nat. Rev. Immunol. 18, 62–76 (2018).
CAS PubMed Google Scholar
- Cordero-Espinoza, L. & Huch, M. The balancing act of the liver: tissue regeneration versus fibrosis. J. Clin. Investig 128, 85–96 (2018).
PubMed Google Scholar
- Pearce, E. J. & MacDonald, A. S. The immunobiology of schistosomiasis. Nat. Rev. Immunol. 2, 499–511 (2002).
CAS PubMed Google Scholar
- He, X. et al. Recombinant adeno-associated virus-mediated inhibition of microRNA-21 protects mice against the lethal schistosome infection by repressing both IL-13 and transforming growth factor beta 1 pathways. Hepatology 61, 2008–2017 (2015).
CAS PubMed PubMed Central Google Scholar
- Gieseck, R. L. 3rd et al. Interleukin-13 activates distinct cellular pathways leading to ductular reaction, steatosis, and fibrosis. Immunity 45, 145–158 (2016).
CAS PubMed PubMed Central Google Scholar
- McDaniel, K. et al. Amelioration of ductular reaction by stem cell derived extracellular vesicles in MDR2 knockout mice via lethal-7 microRNA. Hepatology 69, 2562–2578 (2019).
CAS PubMed PubMed Central Google Scholar
- Hahn, L. et al. IL-13 as target to reduce cholestasis and dysbiosis in Abcb4 knockout mice. Cells 9, 1949 (2020).
CAS PubMed Central Google Scholar
- Walker, J. A. & McKenzie, A. N. J. TH2 cell development and function. Nat. Rev. Immunol. 18, 121–133 (2018).
CAS PubMed Google Scholar
- Gordon, S. & Martinez, F. O. Alternative activation of macrophages: mechanism and functions. Immunity 32, 593–604 (2010).
CAS PubMed Google Scholar
- Su, S. et al. miR-142-5p and miR-130a-3p are regulated by IL-4 and IL-13 and control profibrogenic macrophage program. Nat. Commun. 6, 8523 (2015).
CAS PubMed PubMed Central Google Scholar
- Wang, M. et al. Role of gp91(phox) in hepatic macrophage programming and alcoholic liver disease. Hepatol. Commun. 1, 765–779 (2017).
CAS PubMed PubMed Central Google Scholar
- Goh, Y. P. et al. Eosinophils secrete IL-4 to facilitate liver regeneration. Proc. Natl Acad. Sci. USA 110, 9914–9919 (2013).
CAS PubMed Google Scholar
- Yeung, O. W. et al. Alternatively activated (M2) macrophages promote tumour growth and invasiveness in hepatocellular carcinoma. J. Hepatol. 62, 607–616 (2015).
CAS PubMed Google Scholar
- Zhu, Y. et al. Disruption of tumour-associated macrophage trafficking by the osteopontin-induced colony-stimulating factor-1 signalling sensitises hepatocellular carcinoma to anti-PD-L1 blockade. Gut 68, 1653–1666 (2019).
CAS PubMed Google Scholar
- Brunner, S. M. et al. Tumor-infiltrating, interleukin-33-producing effector-memory CD8(+) T cells in resected hepatocellular carcinoma prolong patient survival. Hepatology 61, 1957–1967 (2015).
CAS PubMed Google Scholar
- Jin, Z. et al. IL-33 released in the liver inhibits tumor growth via promotion of CD4(+) and CD8(+) T cell responses in hepatocellular carcinoma. J. Immunol. 201, 3770–3779 (2018).
CAS PubMed Google Scholar
- Yu, S. J. et al. Targeting the crosstalk between cytokine-induced killer cells and myeloid-derived suppressor cells in hepatocellular carcinoma. J. Hepatol. 70, 449–457 (2019).
CAS PubMed Google Scholar
- Pelaia, C. et al. Interleukin-5 in the pathophysiology of severe asthma. Front Physiol. 10, 1514 (2019).
PubMed PubMed Central Google Scholar
- Molfino, N. A., Gossage, D., Kolbeck, R., Parker, J. M. & Geba, G. P. Molecular and clinical rationale for therapeutic targeting of interleukin-5 and its receptor. Clin. Exp. Allergy 42, 712–737 (2012).
CAS PubMed Google Scholar
- Pelaia, C. et al. Severe eosinophilic asthma: from the pathogenic role of interleukin-5 to the therapeutic action of mepolizumab. Drug Des. Devel Ther. 11, 3137–3144 (2017).
CAS PubMed PubMed Central Google Scholar
- Schwartz, C. et al. Eosinophil-specific deletion of IκBα in mice reveals a critical role of NF-κB-induced Bcl-xL for inhibition of apoptosis. Blood 125, 3896–3904 (2015).
CAS PubMed PubMed Central Google Scholar
- Tiegs, G., Hentschel, J. & Wendel, A. A. T cell-dependent experimental liver injury in mice inducible by concanavalin A. J. Clin. Investig. 90, 196–203 (1992).
CAS PubMed Google Scholar
- Neumann, K. et al. A proinflammatory role of type 2 innate lymphoid cells in murine immune-mediated hepatitis. J. Immunol. 198, 128–137 (2017).
CAS PubMed Google Scholar
- Liu, Z. X., Govindarajan, S., Okamoto, S. & Dennert, G. Fas- and tumor necrosis factor receptor 1-dependent but not perforin-dependent pathways cause injury in livers infected with an adenovirus construct in mice. Hepatology 31, 665–673 (2000).
CAS PubMed Google Scholar
- Peng, H. et al. IL-33 contributes to schistosoma japonicum-induced hepatic pathology through induction of M2 macrophages. Sci. Rep. 6, 29844 (2016).
CAS PubMed PubMed Central Google Scholar
- Sanches, R. C. O. et al. NLRP6 plays an important role in early hepatic immunopathology caused by Schistosoma mansoni infection. Front. Immunol. 11, 795 (2020).
CAS PubMed PubMed Central Google Scholar
- Kaplan, M. H., Hufford, M. M. & Olson, M. R. The development and in vivo function of T helper 9 cells. Nat. Rev. Immunol. 15, 295–307 (2015).
CAS PubMed PubMed Central Google Scholar
- Nowak, E. C. et al. IL-9 as a mediator of Th17-driven inflammatory disease. J. Exp. Med. 206, 1653–1660 (2009).
CAS PubMed PubMed Central Google Scholar
- Townsend, J. M. et al. IL-9-deficient mice establish fundamental roles for IL-9 in pulmonary mastocytosis and goblet cell hyperplasia but not T cell development. Immunity 13, 573–583 (2000).
CAS PubMed Google Scholar
- Jäger, A., Dardalhon, V., Sobel, R. A., Bettelli, E. & Kuchroo, V. K. Th1, Th17, and Th9 effector cells induce experimental autoimmune encephalomyelitis with different pathological phenotypes. J. Immunol. 183, 7169–7177 (2009).
PubMed PubMed Central Google Scholar
- Elyaman, W. et al. IL-9 induces differentiation of TH17 cells and enhances function of FoxP3+ natural regulatory T cells. Proc. Natl Acad. Sci. USA 106, 12885–12890 (2009).
CAS PubMed Google Scholar
- Lu, Y. et al. Th9 cells promote antitumor immune responses in vivo. J. Clin. Investig 122, 4160–4171 (2012).
CAS PubMed Google Scholar
- Clark, R. A. & Schlapbach, C. T(H)9 cells in skin disorders. Semin Immunopathol. 39, 47–54 (2017).
CAS PubMed Google Scholar
- Koch, S., Sopel, N. & Finotto, S. Th9 and other IL-9-producing cells in allergic asthma. Semin Immunopathol. 39, 55–68 (2017).
CAS PubMed Google Scholar
- Guo, X., Cen, Y., Wang, J. & Jiang, H. CXCL10-induced IL-9 promotes liver fibrosis via Raf/MEK/ERK signaling pathway. Biomed. Pharmacother. 105, 282–289 (2018).
CAS PubMed Google Scholar
- Barsoum, R. S., Esmat, G. & El-Baz, T. Human schistosomiasis: clinical perspective: review. J. Adv. Res. 4, 433–444 (2013).
PubMed PubMed Central Google Scholar
- Li, L. et al. Characteristics of IL-9 induced by Schistosoma japonicum infection in C57BL/6 mouse liver. Sci. Rep. 7, 2343 (2017).
PubMed PubMed Central Google Scholar
- Zhan, T. et al. Interleukin-9 blockage reduces early hepatic granuloma formation and fibrosis during Schistosoma japonicum infection in mice. Immunology 158, 296–303 (2019).
CAS PubMed PubMed Central Google Scholar
- Pang, N. et al. TGF-β/Smad signaling pathway positively up-regulates the differentiation of Interleukin-9-producing CD4(+) T cells in human Echinococcus granulosus infection. J. Infect. 76, 406–416 (2018).
PubMed Google Scholar
- Qin, S. Y. et al. A deleterious role for Th9/IL-9 in hepatic fibrogenesis. Sci. Rep. 6, 18694 (2016).
CAS PubMed PubMed Central Google Scholar
- Yu, X. et al. Serum interleukin (IL)-9 and IL-10, but not T-helper 9 (Th9) cells, are associated with survival of patients with acute-on-chronic hepatitis B liver failure. Medicine 95, e3405 (2016).
CAS PubMed PubMed Central Google Scholar
- Ali, M. E. et al. Role of T-helper 9 cells in chronic hepatitis C-infected patients. Viruses 10, 341 (2018).
PubMed Central Google Scholar
- Schmitt, E. & Bopp, T. Amazing IL-9: revealing a new function for an “old” cytokine. J. Clin. Invest 122, 3857–3859 (2012).
CAS PubMed PubMed Central Google Scholar
- Tan, H., Wang, S. & Zhao, L. A tumour-promoting role of Th9 cells in hepatocellular carcinoma through CCL20 and STAT3 pathways. Clin. Exp. Pharmacol. Physiol. 44, 213–221 (2017).
CAS PubMed Google Scholar
- Meng, F. et al. Interleukin-17 signaling in inflammatory, Kupffer cells, and hepatic stellate cells exacerbates liver fibrosis in mice. Gastroenterology 143, 765–776 (2012).
CAS PubMed PubMed Central Google Scholar
- Kolls, J. K. & Linden, A. Interleukin-17 family members and inflammation. Immunity 21, 467–476 (2004).
CAS PubMed Google Scholar
- Iwakura, Y., Ishigame, H., Saijo, S. & Nakae, S. Functional specialization of interleukin-17 family members. Immunity 34, 149–162 (2011).
CAS PubMed Google Scholar
- Gaffen, S. L. Structure and signalling in the IL-17 receptor family. Nat. Rev. Immunol. 9, 556–567 (2009).
CAS PubMed PubMed Central Google Scholar
- Lemmers, A. et al. The interleukin-17 pathway is involved in human alcoholic liver disease. Hepatology 49, 646–657 (2009).
CAS PubMed Google Scholar
- Lafdil, F., Miller, A. M., Ki, S. H. & Gao, B. Th17 cells and their associated cytokines in liver diseases. Cell Mol. Immunol. 7, 250–254 (2010).
CAS PubMed PubMed Central Google Scholar
- Cua, D. J. et al. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 421, 744–748 (2003).
CAS PubMed Google Scholar
- Diveu, C. et al. IL-27 blocks RORc expression to inhibit lineage commitment of Th17 cells. J. Immunol. 182, 5748–5756 (2009).
CAS PubMed Google Scholar
- Hall, A. O., Silver, J. S. & Hunter, C. A. The immunobiology of IL-27. Adv. Immunol. 115, 1–44 (2012).
PubMed Google Scholar
- Liu, Y., Munker, S., Mullenbach, R. & Weng, H. L. IL-13 signaling in liver fibrogenesis. Front Immunol. 3, 116 (2012).
CAS PubMed PubMed Central Google Scholar
- Kleinschek, M. A. et al. IL-25 regulates Th17 function in autoimmune inflammation. J. Exp. Med 204, 161–170 (2007).
CAS PubMed PubMed Central Google Scholar
- Ivanov, I. I. et al. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 126, 1121–1133 (2006).
CAS PubMed Google Scholar
- Yao, Z. et al. Herpesvirus Saimiri encodes a new cytokine, IL-17, which binds to a novel cytokine receptor. Immunity 3, 811–821 (1995).
CAS PubMed Google Scholar
- Andoh, A. et al. IL-17 selectively down-regulates TNF-alpha-induced RANTES gene expression in human colonic subepithelial myofibroblasts. J. Immunol. 169, 1683–1687 (2002).
CAS PubMed Google Scholar
- Moore, E. E. et al. Expression of IL-17B in neurons and evaluation of its possible role in the chromosome 5q-linked form of Charcot-Marie-Tooth disease. Neuromuscul. Disord. 12, 141–150 (2002).
PubMed Google Scholar
- Yamaguchi, Y. et al. IL-17B and IL-17C are associated with TNF-alpha production and contribute to the exacerbation of inflammatory arthritis. J. Immunol. 179, 7128–7136 (2007).
CAS PubMed Google Scholar
- Starnes, T., Broxmeyer, H. E., Robertson, M. J. & Hromas, R. Cutting edge: IL-17D, a novel member of the IL-17 family, stimulates cytokine production and inhibits hemopoiesis. J. Immunol. 169, 642–646 (2002).
CAS PubMed Google Scholar
- Seelige, R., Washington, A. Jr & Bui, J. D. The ancient cytokine IL-17D is regulated by Nrf2 and mediates tumor and virus surveillance. Cytokine 91, 10–12 (2017).
CAS PubMed Google Scholar
- Takatori, H. et al. Lymphoid tissue inducer-like cells are an innate source of IL-17 and IL-22. J. Exp. Med 206, 35–41 (2009).
CAS PubMed PubMed Central Google Scholar
- Lee, J. et al. IL-17E, a novel proinflammatory ligand for the IL-17 receptor homolog IL-17Rh1. J. Biol. Chem. 276, 1660–1664 (2001).
CAS PubMed Google Scholar
- Rickel, E. A. et al. Identification of functional roles for both IL-17RB and IL-17RA in mediating IL-25-induced activities. J. Immunol. 181, 4299–4310 (2008).
CAS PubMed Google Scholar
- Liu, C. et al. A CC’ loop decoy peptide blocks the interaction between Act1 and IL-17RA to attenuate IL-17- and IL-25-induced inflammation. Sci. Signal 4, ra72 (2011).
PubMed PubMed Central Google Scholar
- Giles, D. A. et al. Regulation of inflammation by IL-17A and IL-17F modulates non-alcoholic fatty liver disease pathogenesis. PLoS ONE 11, e0149783 (2016).
PubMed PubMed Central Google Scholar
- von Vietinghoff, S. & Ley, K. IL-17A controls IL-17F production and maintains blood neutrophil counts in mice. J. Immunol. 183, 865–873 (2009).
Google Scholar
- Ma, H. Y. et al. IL-17 signaling in steatotic hepatocytes and macrophages promotes hepatocellular carcinoma in alcohol-related liver disease. J. Hepatol. 72, 946–959 (2020).
CAS PubMed Google Scholar
- Xu, J. et al. Blockade of IL-17 signaling reverses alcohol-induced liver injury and excessive alcohol drinking in mice. JCI Insight 5, e131277 (2020).
PubMed Central Google Scholar
- Ortiz, M. L. et al. Immature myeloid cells directly contribute to skin tumor development by recruiting IL-17-producing CD4+ T cells. J. Exp. Med. 212, 351–367 (2015).
CAS PubMed PubMed Central Google Scholar
- Gomes, A. L. et al. Metabolic inflammation-associated IL-17A causes non-alcoholic steatohepatitis and hepatocellular carcinoma. Cancer Cell 30, 161–175 (2016).
CAS PubMed Google Scholar
- Giles, D. A. et al. Thermoneutral housing exacerbates nonalcoholic fatty liver disease in mice and allows for sex-independent disease modeling. Nat. Med. 23, 829–838 (2017).
CAS PubMed PubMed Central Google Scholar
- Seo, W. et al. Exosome-mediated activation of toll-like receptor 3 in stellate cells stimulates interleukin-17 production by gammadelta T cells in liver fibrosis. Hepatology 64, 616–631 (2016).
CAS PubMed Google Scholar
- Lee, J. H. et al. Mitochondrial double-stranded RNA in exosome promotes interleukin-17 production through toll-like receptor 3 in alcohol-associated liver injury. Hepatology 72, 609–625 (2020).
CAS PubMed Google Scholar
- Kim, J. Y. et al. ER stress drives lipogenesis and steatohepatitis via caspase-2 activation of S1P. Cell 175, 133–145 e15 (2018).
CAS PubMed PubMed Central Google Scholar
- Ikonen, E. Cellular cholesterol trafficking and compartmentalization. Nat. Rev. Mol. Cell Biol. 9, 125–138 (2008).
CAS PubMed Google Scholar
- Osborne, T. F. & Espenshade, P. J. Evolutionary conservation and adaptation in the mechanism that regulates SREBP action: what a long, strange tRIP it’s been. Genes Dev. 23, 2578–2591 (2009).
CAS PubMed PubMed Central Google Scholar
- Fitzky, B. U. et al. 7-Dehydrocholesterol-dependent proteolysis of HMG-CoA reductase suppresses sterol biosynthesis in a mouse model of Smith-Lemli-Opitz/RSH syndrome. J. Clin. Investig. 108, 905–915 (2001).
CAS PubMed Google Scholar
- Yu, H. et al. Selective reconstitution of liver cholesterol biosynthesis promotes lung maturation but does not prevent neonatal lethality in Dhcr7 null mice. BMC Dev. Biol. 7, 27 (2007).
PubMed PubMed Central Google Scholar
- Yu, H., Wessels, A., Tint, G. S. & Patel, S. B. Partial rescue of neonatal lethality of Dhcr7 null mice by a nestin promoter-driven DHCR7 transgene expression. Brain Res. Dev. Brain Res. 156, 46–60 (2005).
CAS PubMed Google Scholar
- Boland, M. R. & Tatonetti, N. P. Investigation of 7-dehydrocholesterol reductase pathway to elucidate off-target prenatal effects of pharmaceuticals: a systematic review. Pharmacogenomics J. 16, 411–429 (2016).
CAS PubMed PubMed Central Google Scholar
- Hueber, W. et al. Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn’s disease: unexpected results of a randomised, double-blind placebo-controlled trial. Gut 61, 1693–1700 (2012).
CAS PubMed PubMed Central Google Scholar
- Solt, L. A. et al. Suppression of TH17 differentiation and autoimmunity by a synthetic ROR ligand. Nature 472, 491–494 (2011).
CAS PubMed PubMed Central Google Scholar
- Ma, H. Y. et al. The role of IL-17 signaling in regulation of the liver-brain axis and intestinal permeability in alcoholic liver disease. Curr. Pathobiol. Rep. 4, 27–35 (2016).
PubMed PubMed Central Google Scholar
- Pascual, M., Balino, P., Aragon, C. M. & Guerri, C. Cytokines and chemokines as biomarkers of ethanol-induced neuroinflammation and anxiety-related behavior: role of TLR4 and TLR2. Neuropharmacology 89, 352–359 (2015).
CAS PubMed Google Scholar
- Chan, A. H. & Schroder, K. Inflammasome signaling and regulation of interleukin-1 family cytokines. J. Exp. Med. 217, e20190314 (2020).
PubMed Google Scholar
- Mantovani, A., Dinarello, C. A., Molgora, M. & Garlanda, C. Interleukin-1 and related cytokines in the regulation of inflammation and immunity. Immunity 50, 778–795 (2019).
CAS PubMed PubMed Central Google Scholar
- Negash, A. A. et al. IL-1beta production through the NLRP3 inflammasome by hepatic macrophages links hepatitis C virus infection with liver inflammation and disease. PLoS Pathog. 9, e1003330 (2013).
CAS PubMed PubMed Central Google Scholar
- Dinarello, C. A. Overview of the IL-1 family in innate inflammation and acquired immunity. Immunol. Rev. 281, 8–27 (2018).
CAS PubMed PubMed Central Google Scholar
- Tilg, H., Moschen, A. R. & Szabo, G. Interleukin-1 and inflammasomes in alcoholic liver disease/acute alcoholic hepatitis and nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Hepatology 64, 955–965 (2016).
CAS PubMed Google Scholar
- Tsutsui, H., Cai, X. & Hayashi, S. Interleukin-1 family cytokines in liver diseases. Mediators Inflamm. 2015, 630265 (2015).
PubMed PubMed Central Google Scholar
- Kamari, Y. et al. Lack of interleukin-1α or interleukin-1β inhibits transformation of steatosis to steatohepatitis and liver fibrosis in hypercholesterolemic mice. J. Hepatol. 55, 1086–1094 (2011).
CAS PubMed PubMed Central Google Scholar
- Almog, T. et al. Interleukin-1α deficiency reduces adiposity, glucose intolerance and hepatic de-novo lipogenesis in diet-induced obese mice. BMJ Open Diabetes Res. Care 7, e000650 (2019).
PubMed PubMed Central Google Scholar
- Olteanu, S. et al. Lack of interleukin-1α in Kupffer cells attenuates liver inflammation and expression of inflammatory cytokines in hypercholesterolaemic mice. Dig. Liver Dis. 46, 433–439 (2014).
CAS PubMed Google Scholar
- Pan, J. et al. Fatty acid activates NLRP3 inflammasomes in mouse Kupffer cells through mitochondrial DNA release. Cell Immunol. 332, 111–120 (2018).
CAS PubMed Google Scholar
- Mirea, A. M. et al. Mice Deficient in the IL-1β activation genes Prtn3, Elane, and Casp1 are protected against the development of obesity-induced NAFLD. Inflammation 43, 1054–1064 (2020).
CAS PubMed PubMed Central Google Scholar
- Cazanave, S. et al. The transcriptomic signature of disease development and progression of nonalcoholic fatty liver disease. Sci. Rep. 7, 17193 (2017).
PubMed PubMed Central Google Scholar
- Xu, B. et al. Gasdermin D plays a key role as a pyroptosis executor of non-alcoholic steatohepatitis in humans and mice. J. Hepatol. 68, 773–782 (2018).
CAS PubMed Google Scholar
- Palomera, L. F. et al. Serum levels of interleukin-1 beta associate better with severity of simple steatosis than liver function tests in morbidly obese patients. J. Res. Med. Sci. 23, 93 (2018).
PubMed PubMed Central Google Scholar
- Yamanishi, K. et al. Interleukin-18-deficient mice develop dyslipidemia resulting in nonalcoholic fatty liver disease and steatohepatitis. Transl. Res. 173, 101–114.e7 (2016).
CAS PubMed Google Scholar
- Murphy, A. J. et al. IL-18 production from the NLRP1 inflammasome prevents obesity and metabolic syndrome. Cell Metab. 23, 155–164 (2016).
CAS PubMed Google Scholar
- Henao-Mejia, J. et al. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature 482, 179–185 (2012).
CAS PubMed PubMed Central Google Scholar
- Flisiak-Jackiewicz, M. et al. Predictive role of interleukin-18 in liver steatosis in obese children. Can. J. Gastroenterol. Hepatol. 2018, 3870454 (2018).
PubMed PubMed Central Google Scholar
- Yasuda, K., Nakanishi, K. & Tsutsui, H. Interleukin-18 in health and disease. Int. J. Mol. Sci. 20, 649 (2019).
- McKie, E. A. et al. A study to investigate the efficacy and safety of an anti-interleukin-18 monoclonal antibody in the treatment of type 2 diabetes mellitus. PLoS ONE 11, e0150018 (2016).
PubMed PubMed Central Google Scholar
- Mridha, A. R. et al. NLRP3 inflammasome blockade reduces liver inflammation and fibrosis in experimental NASH in mice. J. Hepatol. 66, 1037–1046 (2017).
CAS PubMed PubMed Central Google Scholar
- Cai, C. et al. NLRP3 deletion inhibits the non-alcoholic steatohepatitis development and inflammation in Kupffer cells induced by palmitic acid. Inflammation 40, 1875–1883 (2017).
CAS PubMed Google Scholar
- Yang, G., Lee, H. E. & Lee, J. Y. A pharmacological inhibitor of NLRP3 inflammasome prevents non-alcoholic fatty liver disease in a mouse model induced by high fat diet. Sci. Rep. 6, 24399 (2016).
CAS PubMed PubMed Central Google Scholar
- Larsen, C. M. et al. Interleukin-1-receptor antagonist in type 2 diabetes mellitus. N. Engl. J. Med 356, 1517–1526 (2007).
CAS PubMed Google Scholar
- Everett, B. M. et al. Anti-inflammatory therapy with canakinumab for the prevention and management of diabetes. J. Am. Coll. Cardiol. 71, 2392–2401 (2018).
CAS PubMed Google Scholar
- Vasseur, P. et al. Endogenous IL-33 has no effect on the progression of fibrosis during experimental steatohepatitis. Oncotarget 8, 48563–48574 (2017).
PubMed PubMed Central Google Scholar
- Gao, Y. et al. IL-33 treatment attenuated diet-induced hepatic steatosis but aggravated hepatic fibrosis. Oncotarget 7, 33649–33661 (2016).
PubMed PubMed Central Google Scholar
- Giannoudaki, E. et al. Interleukin-36 cytokines alter the intestinal microbiome and can protect against obesity and metabolic dysfunction. Nat. Commun. 10, 4003 (2019).
PubMed PubMed Central Google Scholar
- Ballak, D. B. et al. IL-37 protects against obesity-induced inflammation and insulin resistance. Nat. Commun. 5, 4711 (2014).
CAS PubMed Google Scholar
- Petrasek, J. et al. IL-1 receptor antagonist ameliorates inflammasome-dependent alcoholic steatohepatitis in mice. J. Clin. Investig. 122, 3476–3489 (2012).
CAS PubMed Google Scholar
- Petrasek, J. et al. Metabolic danger signals, uric acid and ATP, mediate inflammatory cross-talk between hepatocytes and immune cells in alcoholic liver disease. J. Leukoc. Biol. 98, 249–256 (2015).
CAS PubMed PubMed Central Google Scholar
- Voican, C. S. et al. Alcohol withdrawal alleviates adipose tissue inflammation in patients with alcoholic liver disease. Liver Int. 35, 967–978 (2015).
CAS PubMed Google Scholar
- Cui, K. et al. Invariant NKT cells promote alcohol-induced steatohepatitis through interleukin-1β in mice. J. Hepatol. 62, 1311–1318 (2015).
CAS PubMed Google Scholar
- Gyongyosi, B. et al. Alcohol-induced IL-17A production in Paneth cells amplifies endoplasmic reticulum stress, apoptosis, and inflammasome-IL-18 activation in the proximal small intestine in mice. Mucosal Immunol. 12, 930–944 (2019).
CAS PubMed PubMed Central Google Scholar
- Khanova, E. et al. Pyroptosis by caspase11/4-gasdermin-D pathway in alcoholic hepatitis in mice and patients. Hepatology 67, 1737–1753 (2018).
CAS PubMed PubMed Central Google Scholar
- Iracheta-Vellve, A. et al. Interleukin-1 inhibition facilitates recovery from liver injury and promotes regeneration of hepatocytes in alcoholic hepatitis in mice. Liver Int. 37, 968–973 (2017).
CAS PubMed PubMed Central Google Scholar
- NIH U.S. National Library of Medicine. ClinicalTrials.gov. Efficacy Study of Anakinra, Pentoxifylline, and Zinc Compared to Methylprednisolone in Severe Acute Alcoholic Hepatitis. https://clinicaltrials.gov/ct2/show/NCT01809132.
- McHedlidze, T. et al. Interleukin-33-dependent innate lymphoid cells mediate hepatic fibrosis. Immunity 39, 357–371 (2013).
CAS PubMed PubMed Central Google Scholar
- Marvie, P. et al. Interleukin-33 overexpression is associated with liver fibrosis in mice and humans. J. Cell Mol. Med. 14, 1726–1739 (2010).
CAS PubMed Google Scholar
- Sun, Z. et al. Plasma levels of soluble ST2, but not IL-33, correlate with the severity of alcoholic liver disease. J. Cell Mol. Med. 23, 887–897 (2019).
CAS PubMed Google Scholar
- Artru, F. et al. IL-33/ST2 pathway regulates neutrophil migration and predicts outcome in patients with severe alcoholic hepatitis. J. Hepatol. 72, 1052–1061 (2020).
CAS PubMed Google Scholar
- Grabherr, F. et al. Ethanol-mediated suppression of IL-37 licenses alcoholic liver disease. Liver Int 38, 1095–1101 (2018).
CAS PubMed Google Scholar
- Gieling, R. G., Wallace, K. & Han, Y. P. Interleukin-1 participates in the progression from liver injury to fibrosis. Am. J. Physiol. Gastrointest. Liver Physiol. 296, G1324–G1331 (2009).
CAS PubMed PubMed Central Google Scholar
- Wree, A. et al. NLRP3 inflammasome driven liver injury and fibrosis: Roles of IL-17 and TNF in mice. Hepatology 67, 736–749 (2018).
CAS PubMed Google Scholar
- Meier, R. P. H. et al. Interleukin-1 receptor antagonist modulates liver inflammation and fibrosis in mice in a model-dependent manner. Int J. Mol. Sci. 20, 1295 (2019).
CAS PubMed Central Google Scholar
- Monteiro, S. et al. Differential inflammasome activation predisposes to acute-on-chronic liver failure in human and experimental cirrhosis with and without previous decompensation. Gut (2020). in press, https://doi.org/10.1136/gutjnl-2019-320170.
- Kotsiou, O. S., Gourgoulianis, K. I. & Zarogiannis, S. G. IL-33/ST2 axis in organ fibrosis. Front Immunol. 9, 2432 (2018).
PubMed PubMed Central Google Scholar
- Tan, Z. et al. Interleukin-33 drives hepatic fibrosis through activation of hepatic stellate cells. Cell Mol. Immunol. 15, 388–398 (2018).
CAS PubMed Google Scholar
- Sultan, M. et al. Interleukin-1α and Interleukin-1β play a central role in the pathogenesis of fulminant hepatic failure in mice. PLoS ONE 12, e0184084 (2017).
PubMed PubMed Central Google Scholar
- Gehrke, N. et al. Hepatocyte-specific deletion of IL1-RI attenuates liver injury by blocking IL-1 driven autoinflammation. J. Hepatol. 68, 986–995 (2018).
CAS PubMed Google Scholar
- Zhang, C. et al. Macrophage-derived IL-1α promotes sterile inflammation in a mouse model of acetaminophen hepatotoxicity. Cell Mol. Immunol. 15, 973–982 (2018).
CAS PubMed Google Scholar
- Bachmann, M., Pfeilschifter, J. & Mühl, H. A prominent role of interleukin-18 in acetaminophen-induced liver injury advocates its blockage for therapy of hepatic necroinflammation. Front. Immunol. 9, 161 (2018).
PubMed PubMed Central Google Scholar
- Castillo-Dela Cruz, P. et al. Intestinal IL-17R signaling constrains IL-18-driven liver inflammation by the regulation of microbiome-derived products. Cell Rep. 29, 2270–2283.e7 (2019).
CAS PubMed Google Scholar
- Antunes, M. M. et al. IL-33 signalling in liver immune cells enhances drug-induced liver injury and inflammation. Inflamm. Res. 67, 77–88 (2018).
CAS PubMed Google Scholar
- Yazdani, H. O. et al. IL-33 exacerbates liver sterile inflammation by amplifying neutrophil extracellular trap formation. J. Hepatol. 68, 130–139 (2018).
- Scheiermann, P. et al. Application of IL-36 receptor antagonist weakens CCL20 expression and impairs recovery in the late phase of murine acetaminophen-induced liver injury. Sci. Rep. 5, 8521 (2015).
CAS PubMed PubMed Central Google Scholar
- Feng, X. X. et al. IL-37 suppresses the sustained hepatic IFN-γ/TNF-α production and T cell-dependent liver injury. Int Immunopharmacol. 69, 184–193 (2019).
CAS PubMed Google Scholar
- Lin, C. I., Tsao, C. C. & Chuang, Y. H. IL-37 increases liver inflammation in Con A-induced hepatitis by increasing IFN-γ secretion of infiltrated NK Cells. J. Immunol. 204, 238.12 (2020).
Google Scholar
- Fazel Modares, N. et al. IL-6 trans-signaling controls liver regeneration after partial hepatectomy. Hepatology 70, 2075–2091 (2019).
CAS PubMed Google Scholar
- Lokau, J. et al. Proteolytic cleavage governs interleukin-11 trans-signaling. Cell Rep. 14, 1761–1773 (2016).
CAS PubMed Google Scholar
- Jones, S. A., Scheller, J. & Rose-John, S. Therapeutic strategies for the clinical blockade of IL-6/gp130 signaling. J. Clin. Investig. 121, 3375–3383 (2011).
CAS PubMed Google Scholar
- Norris, C. A. et al. Synthesis of IL-6 by hepatocytes is a normal response to common hepatic stimuli. PLoS ONE 9, e96053 (2014).
PubMed PubMed Central Google Scholar
- Schmidt-Arras, D. & Rose-John, S. IL-6 pathway in the liver: from physiopathology to therapy. J. Hepatol. 64, 1403–1415 (2016).
CAS PubMed Google Scholar
- Gao, R. Y. et al. Hypoxia-inducible factor-2alpha reprograms liver macrophages to protect against acute liver injury through the production of interleukin-6. Hepatology 71, 2105–2117 (2020).
CAS PubMed Google Scholar
- Zhang, X. et al. Interleukin-6 is an important mediator for mitochondrial DNA repair after alcoholic liver injury in mice. Hepatology 52, 2137–2147 (2010).
CAS PubMed PubMed Central Google Scholar
- Miller, A. M. et al. Inflammation-associated interleukin-6/signal transducer and activator of transcription 3 activation ameliorates alcoholic and nonalcoholic fatty liver diseases in interleukin-10-deficient mice. Hepatology 54, 846–856 (2011).
CAS PubMed PubMed Central Google Scholar
- Mas, E. et al. IL-6 deficiency attenuates murine diet-induced non-alcoholic steatohepatitis. PLoS One 4, e7929 (2009).
PubMed PubMed Central Google Scholar
- Xu, M. J. et al. Liver is the major source of elevated serum lipocalin-2 levels after bacterial infection or partial hepatectomy: a critical role for IL-6/STAT3. Hepatology 61, 692–702 (2015).
CAS PubMed PubMed Central Google Scholar
- Aleksandrova, K. et al. Inflammatory and metabolic biomarkers and risk of liver and biliary tract cancer. Hepatology 60, 858–871 (2014).
CAS PubMed PubMed Central Google Scholar
- Wan, S. et al. Tumor-associated macrophages produce interleukin 6 and signal via STAT3 to promote expansion of human hepatocellular carcinoma stem cells. Gastroenterology 147, 1393–1404 (2014).
CAS PubMed PubMed Central Google Scholar
- Bergmann, J. et al. IL-6 trans-signaling is essential for the development of hepatocellular carcinoma in mice. Hepatology 65, 89–103 (2017).
CAS PubMed Google Scholar
- Isorce, N. et al. Antiviral activity of various interferons and pro-inflammatory cytokines in non-transformed cultured hepatocytes infected with hepatitis B virus. Antivir. Res. 130, 36–45 (2016).
CAS PubMed Google Scholar
- Faure-Dupuy, S. et al. Hepatitis B virus-induced modulation of liver macrophage function promotes hepatocyte infection. J. Hepatol. 71, 1086–1098 (2019).
CAS PubMed Google Scholar
- Lan, T., Chang, L., Wu, L. & Yuan, Y. F. IL-6 plays a crucial role in HBV infection. J. Clin. Transl. Hepatol. 3, 271–276 (2015).
PubMed PubMed Central Google Scholar
- Cao, Y. et al. IL-27, a cytokine, and IFN-lambda1, a type III IFN, are coordinated to regulate virus replication through type I IFN. J. Immunol. 192, 691–703 (2014).
CAS PubMed Google Scholar
- Negash, A. A., Olson, R. M., Griffin, S. & Gale, M. Jr Modulation of calcium signaling pathway by hepatitis C virus core protein stimulates NLRP3 inflammasome activation. PLoS Pathog. 15, e1007593 (2019).
CAS PubMed PubMed Central Google Scholar
- Larrea, E. et al. Characterization of the CD40L/Oncostatin M/Oncostatin M receptor axis as an antiviral and immunostimulatory system disrupted in chronic HCV infection. J. Hepatol. 60, 482–489 (2014).
CAS PubMed Google Scholar
- Yu, J., Feng, Z., Tan, L., Pu, L. & Kong, L. Interleukin-11 protects mouse liver from warm ischemia/reperfusion (WI/Rp) injury. Clin. Res Hepatol. Gastroenterol. 40, 562–570 (2016).
CAS PubMed Google Scholar
- Widjaja, A. A. et al. Inhibiting interleukin 11 signaling reduces hepatocyte death and liver fibrosis, inflammation, and steatosis in mouse models of nonalcoholic steatohepatitis. Gastroenterology 157, 777–792 e14 (2019).
CAS PubMed Google Scholar
- Foglia, B. et al. Oncostatin M, A profibrogenic mediator overexpressed in non-alcoholic fatty liver disease, stimulates migration of hepatic myofibroblasts. Cells 9, 28 (2019).
PubMed Central Google Scholar
- Matsuda, M. et al. Oncostatin M causes liver fibrosis by regulating cooperation between hepatic stellate cells and macrophages in mice. Hepatology 67, 296–312 (2018).
CAS PubMed Google Scholar
- Cui, M. X. et al. Alleviative effect of ciliary neurotrophic factor analogue on high fat-induced hepatic steatosis is partially independent of the central regulation. Clin. Exp. Pharmacol. Physiol. 44, 395–402 (2017).
CAS PubMed Google Scholar
- Nonogaki, K. et al. LIF and CNTF, which share the gp130 transduction system, stimulate hepatic lipid metabolism in rats. Am. J. Physiol. 271, E521–E528 (1996).
CAS PubMed Google Scholar
- Guillot, A. et al. Interleukins-17 and 27 promote liver regeneration by sequentially inducing progenitor cell expansion and differentiation. Hepatol. Commun. 2, 329–343 (2018).
CAS PubMed PubMed Central Google Scholar
- Lopez-Yoldi, M., Moreno-Aliaga, M. J. & Bustos, M. Cardiotrophin-1: a multifaceted cytokine. Cytokine Growth Factor Rev. 26, 523–532 (2015).
CAS PubMed Google Scholar
- Dudakov, J. A., Hanash, A. M. & van den Brink, M. R. Interleukin-22: immunobiology and pathology. Annu Rev. Immunol. 33, 747–785 (2015).
CAS PubMed PubMed Central Google Scholar
- Sabat, R., Ouyang, W. & Wolk, K. Therapeutic opportunities of the IL-22-IL-22R1 system. Nat. Rev. Drug Disco. 13, 21–38 (2014).
CAS Google Scholar
- Rutz, S., Eidenschenk, C. & Ouyang, W. IL-22, not simply a Th17 cytokine. Immunol. Rev. 252, 116–132 (2013).
PubMed Google Scholar
- Sabat, R. IL-10 family of cytokines. Cytokine Growth Factor Rev. 21, 315–324 (2010).
CAS PubMed Google Scholar
- Radaeva, S., Sun, R., Pan, H. N., Hong, F. & Gao, B. Interleukin 22 (IL-22) plays a protective role in T cell-mediated murine hepatitis: IL-22 is a survival factor for hepatocytes via STAT3 activation. Hepatology 39, 1332–1342 (2004).
CAS PubMed Google Scholar
- Feng, D. et al. Interleukin-22 promotes proliferation of liver stem/progenitor cells in mice and patients with chronic hepatitis B virus infection. Gastroenterology 143, 188–98 e7 (2012).
CAS PubMed PubMed Central Google Scholar
- Kong, X. et al. Interleukin-22 induces hepatic stellate cell senescence and restricts liver fibrosis in mice. Hepatology 56, 1150–1159 (2012).
CAS PubMed PubMed Central Google Scholar
- Lejeune, D. et al. Interleukin-22 (IL-22) activates the JAK/STAT, ERK, JNK, and p38 MAP kinase pathways in a rat hepatoma cell line. Pathways that are shared with and distinct from IL-10. J. Biol. Chem. 277, 33676–33682 (2002).
CAS PubMed Google Scholar
- Zheng, Y. et al. Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens. Nat. Med. 14, 282–289 (2008).
CAS PubMed Google Scholar
- Zheng, M. et al. Therapeutic role of interleukin 22 in experimental intra-abdominal Klebsiella pneumoniae infection in mice. Infect. Immun. 84, 782–789 (2016).
CAS PubMed PubMed Central Google Scholar
- Liang, S. C. et al. IL-22 induces an acute-phase response. J. Immunol. 185, 5531–5538 (2010).
CAS PubMed Google Scholar
- Xing, W. W. et al. Hepatoprotective effects of IL-22 on fulminant hepatic failure induced by d-galactosamine and lipopolysaccharide in mice. Cytokine 56, 174–179 (2011).
CAS PubMed Google Scholar
- Park, O. et al. In vivo consequences of liver-specific interleukin-22 expression in mice: Implications for human liver disease progression. Hepatology 54, 252–261 (2011).
PubMed PubMed Central Google Scholar
- Ashour, T. H. Therapy with interleukin-22 alleviates hepatic injury and hemostasis dysregulation in rat model of acute liver failure. Adv. Hematol. 2014, 705290 (2014).
PubMed PubMed Central Google Scholar
- Wahl, C., Wegenka, U. M., Leithauser, F., Schirmbeck, R. & Reimann, J. IL-22-dependent attenuation of T cell-dependent (ConA) hepatitis in herpes virus entry mediator deficiency. J. Immunol. 182, 4521–4528 (2009).
CAS PubMed Google Scholar
- Abe, H. et al. Aryl hydrocarbon receptor plays protective roles in ConA-induced hepatic injury by both suppressing IFN-gamma expression and inducing IL-22. Int Immunol. 26, 129–137 (2014).
CAS PubMed Google Scholar
- Zenewicz, L. A. et al. Interleukin-22 but not interleukin-17 provides protection to hepatocytes during acute liver inflammation. Immunity 27, 647–659 (2007).
CAS PubMed PubMed Central Google Scholar
- Scheiermann, P. et al. Application of interleukin-22 mediates protection in experimental acetaminophen-induced acute liver injury. Am. J. Pathol. 182, 1107–1113 (2013).
CAS PubMed Google Scholar
- Feng, D. et al. Acute and chronic effects of IL-22 on acetaminophen-induced liver injury. J. Immunol. 193, 2512–2518 (2014).
CAS PubMed PubMed Central Google Scholar
- Pan, H., Hong, F., Radaeva, S. & Gao, B. Hydrodynamic gene delivery of interleukin-22 protects the mouse liver from concanavalin A-, carbon tetrachloride-, and Fas ligand-induced injury via activation of STAT3. Cell Mol. Immunol. 1, 43–49 (2004).
CAS PubMed Google Scholar
- Mo, R. et al. Enhanced autophagy contributes to protective effects of IL-22 against acetaminophen-induced liver injury. Theranostics 8, 4170–4180 (2018).
CAS PubMed PubMed Central Google Scholar
- Lai, R. et al. Protective effect of Th22 cells and intrahepatic IL-22 in drug induced hepatocellular injury. J. Hepatol. 63, 148–155 (2015).
CAS PubMed Google Scholar
- Ki, S. H. et al. Interleukin-22 treatment ameliorates alcoholic liver injury in a murine model of chronic-binge ethanol feeding: role of signal transducer and activator of transcription 3. Hepatology 52, 1291–1300 (2010).
CAS PubMed PubMed Central Google Scholar
- Meng, F. et al. Interleukin-17 signaling in inflammatory, Kupffer cells, and hepatic stellate cells exacerbates liver fibrosis in mice. Gastroenterology 143, 765–776 e3 (2012).
CAS PubMed PubMed Central Google Scholar
- Hu, B. L. et al. Interleukin-22 ameliorates liver fibrosis through miR-200a/beta-catenin. Sci. Rep. 6, 36436 (2016).
CAS PubMed PubMed Central Google Scholar
- Sertorio, M. et al. IL-22 and IL-22 binding protein (IL-22BP) regulate fibrosis and cirrhosis in hepatitis C virus and schistosome infections. Hepatology 61, 1321–1331 (2015).
CAS PubMed Google Scholar
- Fabre, T. et al. Type 3 cytokines IL-17A and IL-22 drive TGF-beta-dependent liver fibrosis. Sci Immunol. 3 (2018).
- Wu, L. Y. et al. Up-regulation of interleukin-22 mediates liver fibrosis via activating hepatic stellate cells in patients with hepatitis C. Clin. Immunol. 158, 77–87 (2015).
CAS PubMed Google Scholar
- Brand, S. et al. IL-22-mediated liver cell regeneration is abrogated by SOCS-1/3 overexpression in vitro. Am. J. Physiol. Gastrointest. Liver Physiol. 292, G1019–G1028 (2007).
CAS PubMed Google Scholar
- Zhou, H. et al. Enhanced regeneration and hepatoprotective effects of interleukin 22 fusion protein on a predamaged liver undergoing partial hepatectomy. J. Immunol. Res. 2018, 5241526 (2018).
PubMed PubMed Central Google Scholar
- Mo, R. et al. Persistently elevated circulating Th22 reversely correlates with prognosis in HBV-related acute-on-chronic liver failure. J. Gastroenterol. Hepatol. 32, 677–686 (2017).
CAS PubMed Google Scholar
- Schwarzkopf, K. et al. IL-22 and IL-22-binding protein are associated with development of and mortality from acute-on-chronic liver failure. Hepatol. Commun. 3, 392–405 (2019).
CAS PubMed PubMed Central Google Scholar
- Yang, L. et al. Amelioration of high fat diet induced liver lipogenesis and hepatic steatosis by interleukin-22. J. Hepatol. 53, 339–347 (2010).
CAS PubMed Google Scholar
- Zhang, Y. et al. A proinflammatory role for interleukin-22 in the immune response to hepatitis B virus. Gastroenterology 141, 1897–1906 (2011).
CAS PubMed PubMed Central Google Scholar
- Foster, R. G., Golden-Mason, L., Rutebemberwa, A. & Rosen, H. R. Interleukin (IL)-17/IL-22-producing T cells enriched within the liver of patients with chronic hepatitis C viral (HCV) infection. Dig. Dis. Sci. 57, 381–389 (2012).
CAS PubMed Google Scholar
- Zhang, J. Y. et al. Interleukin-17-producing CD4(+) T cells increase with severity of liver damage in patients with chronic hepatitis B. Hepatology 51, 81–91 (2010).
CAS PubMed Google Scholar
- Chang, Q. et al. Th17 cells are increased with severity of liver inflammation in patients with chronic hepatitis C. J. Gastroenterol. Hepatol. 27, 273–278 (2012).
CAS PubMed Google Scholar
- Zhao, J. et al. Pathological functions of interleukin-22 in chronic liver inflammation and fibrosis with hepatitis B virus infection by promoting T helper 17 cell recruitment. Hepatology 59, 1331–1342 (2014).
CAS PubMed PubMed Central Google Scholar
- Dambacher, J. et al. The role of interleukin-22 in hepatitis C virus infection. Cytokine 41, 209–216 (2008).
CAS PubMed Google Scholar
- Jiang, R. et al. Interleukin-22 promotes human hepatocellular carcinoma by activation of STAT3. Hepatology 54, 900–909 (2011).
CAS PubMed Google Scholar
- Shi, J. et al. Interleukin 22 is related to development and poor prognosis of hepatocellular carcinoma. Clin. Res. Hepatol. Gastroenterol. (2020). in press, https://doi.org/10.1016/j.clinre.2020.01.009.
- Waidmann, O. et al. Interleukin-22 serum levels are a negative prognostic indicator in patients with hepatocellular carcinoma. Hepatology 59, 1207 (2014).
CAS PubMed Google Scholar
- Tang, K. Y. et al. Safety, pharmacokinetics, and biomarkers of F-652, a recombinant human interleukin-22 dimer, in healthy subjects. Cell Mol. Immunol. 16, 473–482 (2019).
CAS PubMed Google Scholar
- Rothenberg, M. E. et al. Randomized Phase I healthy volunteer study of UTTR1147A (IL-22Fc): a potential therapy for epithelial injury. Clin. Pharmacol. Ther. 105, 177–189 (2019).
CAS PubMed Google Scholar
- Arab, J. P. et al. An open-label, dose-escalation study to assess the safety and efficacy of IL-22 agonist F-652 in patients with alcohol-associated hepatitis. Hepatology 72, 441–453 (2019).
Google Scholar
- Xiang, X., Hwang, S., Feng, D., Shah, V. H. & Gao, B. Interleukin-22 in alcoholic hepatitis and beyond. Hepatol. Int 14, 667–676 (2020).
PubMed Google Scholar
- Wolk, K., Kunz, S., Asadullah, K. & Sabat, R. Cutting edge: immune cells as sources and targets of the IL-10 family members? J. Immunol. 168, 5397–5402 (2002).
CAS PubMed Google Scholar
- Wegenka, U. M., Dikopoulos, N., Reimann, J., Adler, G. & Wahl, C. The murine liver is a potential target organ for IL-19, IL-20 and IL-24: Type I interferons and LPS regulate the expression of IL-20R2. J. Hepatol. 46, 257–265 (2007).
CAS PubMed Google Scholar
- Hsu, Y. H. et al. Interleukin-19 mediates tissue damage in murine ischemic acute kidney injury. PLoS ONE 8, e56028 (2013).
CAS PubMed PubMed Central Google Scholar
- Blumberg, H. et al. Interleukin 20: discovery, receptor identification, and role in epidermal function. Cell 104, 9–19 (2001).
CAS PubMed Google Scholar
- Caparros, E. & Frances, R. The interleukin-20 cytokine family in liver disease. Front. Immunol. 9, 1155 (2018).
PubMed PubMed Central Google Scholar
- Chiu, Y. S., Wei, C. C., Lin, Y. J., Hsu, Y. H. & Chang, M. S. IL-20 and IL-20R1 antibodies protect against liver fibrosis. Hepatology 60, 1003–1014 (2014).
CAS PubMed Google Scholar
- Ding, W. Z. et al. Anti-IL-20 monoclonal antibody suppresses hepatocellular carcinoma progression. Oncol. Lett. 16, 6156–6162 (2018).
CAS PubMed PubMed Central Google Scholar
- Chiu, Y. S. et al. Anti-IL-20 monoclonal antibody inhibited tumor growth in hepatocellular carcinoma. Sci. Rep. 7, 17609 (2017).
PubMed PubMed Central Google Scholar
- Menezes, M. E. et al. MDA-7/IL-24: multifunctional cancer killing cytokine. Adv. Exp. Med Biol. 818, 127–153 (2014).
CAS PubMed PubMed Central Google Scholar
- Chen, W. Y. et al. IL-24 inhibits the growth of hepatoma cells in vivo. Genes Immun. 6, 493–499 (2005).
CAS PubMed Google Scholar
- Wang, C. J. et al. Interferon-alpha enhances antitumor activities of oncolytic adenovirus-mediated IL-24 expression in hepatocellular carcinoma. Mol. Cancer 11, 31 (2012).
CAS PubMed PubMed Central Google Scholar
- Liu, X. et al. Gene-viro-therapy targeting liver cancer by a dual-regulated oncolytic adenoviral vector harboring IL-24 and TRAIL. Cancer Gene Ther. 19, 49–57 (2012).
PubMed Google Scholar
- Tong, A. W. et al. Intratumoral injection of INGN 241, a nonreplicating adenovector expressing the melanoma-differentiation associated gene-7 (mda-7/IL24): biologic outcome in advanced cancer patients. Mol. Ther. 11, 160–172 (2005).
CAS PubMed Google Scholar
- Cunningham, C. C. et al. Clinical and local biological effects of an intratumoral injection of mda-7 (IL24; INGN 241) in patients with advanced carcinoma: a phase I study. Mol. Ther. 11, 149–159 (2005).
CAS PubMed Google Scholar
- Fisher, P. B. et al. mda-7/IL-24, a novel cancer selective apoptosis inducing cytokine gene: from the laboratory into the clinic. Cancer Biol. Ther. 2, S23–S37 (2003).
CAS PubMed Google Scholar
- Wang, J. et al. Intracellular XBP1-IL-24 axis dismantles cytotoxic unfolded protein response in the liver. Cell Death Dis. 11, 17 (2020).
PubMed PubMed Central Google Scholar
- Knappe, A., Hor, S., Wittmann, S. & Fickenscher, H. Induction of a novel cellular homolog of interleukin-10, AK155, by transformation of T lymphocytes with herpesvirus saimiri. J. Virol. 74, 3881–3887 (2000).
CAS PubMed PubMed Central Google Scholar
- Hor, S. et al. The T-cell lymphokine interleukin-26 targets epithelial cells through the interleukin-20 receptor 1 and interleukin-10 receptor 2 chains. J. Biol. Chem. 279, 33343–33351 (2004).
PubMed Google Scholar
- Miot, C. et al. IL-26 is overexpressed in chronically HCV-infected patients and enhances TRAIL-mediated cytotoxicity and interferon production by human NK cells. Gut 64, 1466–1475 (2015).
CAS PubMed Google Scholar
- Xi, Z. F. et al. Expression of IL-26 predicts prognosis of patients with hepatocellular carcinoma after surgical resection. Hepatobiliary Pancreat. Dis. Int 18, 242–248 (2019).
PubMed Google Scholar
- Hu, Z. et al. miRNA-132-3p inhibits osteoblast differentiation by targeting Ep300 in simulated microgravity. Sci. Rep. 5, 18655 (2015).
CAS PubMed PubMed Central Google Scholar
- Schmitz, J. et al. IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity 23, 479–490 (2005).
CAS PubMed Google Scholar
- Arshad, M. I. et al. TRAIL but not FasL and TNFalpha, regulates IL-33 expression in murine hepatocytes during acute hepatitis. Hepatology 56, 2353–2362 (2012).
CAS PubMed Google Scholar
- von Freeden-Jeffry, U. et al. Lymphopenia in interleukin (IL)-7 gene-deleted mice identifies IL-7 as a nonredundant cytokine. J. Exp. Med. 181, 1519–1526 (1995).
Google Scholar
- Sawa, Y. et al. Hepatic interleukin-7 expression regulates T cell responses. Immunity 30, 447–457 (2009).
CAS PubMed Google Scholar
- Liang, B. et al. Role of hepatocyte-derived IL-7 in maintenance of intrahepatic NKT cells and T cells and development of B cells in fetal liver. J. Immunol. 189, 4444–4450 (2012).
CAS PubMed Google Scholar
- Nishina, T. et al. Interleukin-11 links oxidative stress and compensatory proliferation. Sci. Signal 5, ra5 (2012).
PubMed Google Scholar