Fibrotic disease and the TH1/TH2 paradigm (original) (raw)

• Cotran, R. S., Kumar, V. & Collins, T. in Pathologic Basis of Disease Vol. 6 (eds Cotran, R. S., Kumar, V. & Collins, T.) 89–112 (W. B. Saunders Company, Philadelphia, 1999).
  Google Scholar
• Wynn, T. A. et al. An IL-12-based vaccination method for preventing fibrosis induced by schistosome infection. Nature 376, 594–596 (1995). An early example of the opposing activities of T H 1 and T H 2 responses in a progressive fibrotic disease.
  Article CAS PubMed Google Scholar
• Hoffmann, K. F., Cheever, A. W. & Wynn, T. A. IL-10 and the dangers of immune polarization: excessive type 1 and type 2 cytokine responses induce distinct forms of lethal immunopathology in murine schistosomiasis. J. Immunol. 164, 6406–6416 (2000).
  Article CAS PubMed Google Scholar
• Gurujeyalakshmi, G. & Giri, S. N. Molecular mechanisms of antifibrotic effect of interferon-γ in bleomycin-mouse model of lung fibrosis: downregulation of TGF-β and procollagen I and III gene expression. Exp. Lung Res. 21, 791–808 (1995).
  Article CAS PubMed Google Scholar
• Keane, M. P., Belperio, J. A., Burdick, M. D. & Strieter, R. M. IL-12 attenuates bleomycin-induced pulmonary fibrosis. Am. J. Physiol. Lung Cell. Mol. Physiol. 281, L92–L97 (2001).
  Article CAS PubMed Google Scholar
• Oldroyd, S. D., Thomas, G. L., Gabbiani, G. & El Nahas, A. M. Interferon-γ inhibits experimental renal fibrosis. Kidney Int. 56, 2116–2127 (1999).
  Article CAS PubMed Google Scholar
• Poynard, T., Yuen, M. F., Ratziu, V. & Lai, C. L. Viral hepatitis C. Lancet 362, 2095–2100 (2003).
  Article CAS PubMed Google Scholar
• Hesse, M., Cheever, A. W., Jankovic, D. & Wynn, T. A. NOS-2 mediates the protective anti-inflammatory and antifibrotic effects of the TH1-inducing adjuvant, IL-12, in a TH2 model of granulomatous disease. Am. J. Pathol. 157, 945–955 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Hoffmann, K. F. et al. Disease fingerprinting with cDNA microarrays reveals distinct gene expression profiles in lethal type 1 and type 2 cytokine-mediated inflammatory reactions. FASEB J. 15, 2545–2547 (2001).
  Article CAS PubMed Google Scholar
• Sandler, N. G., Mentink-Kane, M. M., Cheever, A. W. & Wynn, T. A. Global gene expression profiles during acute pathogen-induced pulmonary inflammation reveal divergent roles for TH1 and TH2 responses in tissue repair. J. Immunol. 171, 3655–3667 (2003).
  Article CAS PubMed Google Scholar
• Walker, L. S. & Abbas, A. K. The enemy within: keeping self-reactive T cells at bay in the periphery. Nature Rev. Immunol. 2, 11–19 (2002).
  Article CAS Google Scholar
• Hesse, M. et al. Differential regulation of nitric oxide synthase-2 and arginase-1 by type 1/type 2 cytokines in vivo: granulomatous pathology is shaped by the pattern of L-arginine metabolism. J. Immunol. 167, 6533–6544 (2001). The first report to show a functional link between T H 1/T H 2 responses and NOS2/ARG1 activity in an experimental model of fibrosis.
  Article CAS PubMed Google Scholar
• Decitre, M. et al. Lysyl oxidase-like protein localizes to sites of de novo fibrinogenesis in fibrosis and in the early stromal reaction of ductal breast carcinomas. Lab. Invest. 78, 143–151 (1998).
  CAS PubMed Google Scholar
• Wang, S. & Hirschberg, R. BMP7 antagonizes TGF-β-dependent fibrogenesis in mesangial cells. Am. J. Physiol. Renal Physiol. 284, F1006–F1013 (2003).
  Article CAS PubMed Google Scholar
• Underwood, D. C. et al. SB 239063, a p38 MAPK inhibitor, reduces neutrophilia, inflammatory cytokines, MMP-9, and fibrosis in lung. Am. J. Physiol. Lung Cell. Mol. Physiol. 279, L895–L902 (2000).
  Article CAS PubMed Google Scholar
• Kim, H. et al. TIMP-1 deficiency does not attenuate interstitial fibrosis in obstructive nephropathy. J. Am. Soc. Nephrol. 12, 736–748 (2001).
  CAS PubMed Google Scholar
• Vaillant, B., Chiaramonte, M. G., Cheever, A. W., Soloway, P. D. & Wynn, T. A. Regulation of hepatic fibrosis and extracellular matrix genes by the TH response: new insight into the role of tissue inhibitors of matrix metalloproteinases. J. Immunol. 167, 7017–7026 (2001).
  Article CAS PubMed Google Scholar
• Kaminski, N. et al. Global analysis of gene expression in pulmonary fibrosis reveals distinct programs regulating lung inflammation and fibrosis. Proc. Natl Acad. Sci. USA 97, 1778–1783 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Kristensen, D. B. et al. Proteome analysis of rat hepatic stellate cells. Hepatology 32, 268–277 (2000).
  Article CAS PubMed Google Scholar
• Emura, M. et al. In vitro production of B cell growth factor and B cell differentiation factor by peripheral blood mononuclear cells and bronchoalveolar lavage T lymphocytes from patients with idiopathic pulmonary fibrosis. Clin. Exp. Immunol. 82, 133–139 (1990).
  Article CAS PubMed PubMed Central Google Scholar
• Wallace, W. A., Ramage, E. A., Lamb, D. & Howie, S. E. A type 2 (TH2-like) pattern of immune response predominates in the pulmonary interstitium of patients with cryptogenic fibrosing alveolitis (CFA). Clin. Exp. Immunol. 101, 436–441 (1995).
  Article CAS PubMed PubMed Central Google Scholar
• Booth, M. et al. Periportal fibrosis in human Schistosoma mansoni infection is associated with low IL-10, low IFN-γ, high TNF-α, or low RANTES, depending on age and gender. J. Immunol. 172, 1295–1303 (2004).
  Article CAS PubMed Google Scholar
• Buttner, C. et al. Local production of interleukin-4 during radiation-induced pneumonitis and pulmonary fibrosis in rats: macrophages as a prominent source of interleukin-4. Am. J. Respir. Cell Mol. Biol. 17, 315–325 (1997).
  Article CAS PubMed Google Scholar
• Fertin, C. et al. Interleukin-4 stimulates collagen synthesis by normal and scleroderma fibroblasts in dermal equivalents. Cell. Mol. Biol. 37, 823–829 (1991).
  CAS PubMed Google Scholar
• Letterio, J. J. & Roberts, A. B. Regulation of immune responses by TGF-β. Annu. Rev. Immunol. 16, 137–161 (1998). A comprehensive review of the biological activities of TGF-β in health and disease.
  Article CAS PubMed Google Scholar
• Sempowski, G. D., Beckmann, M. P., Derdak, S. & Phipps, R. P. Subsets of murine lung fibroblasts express membrane-bound and soluble IL-4 receptors. Role of IL-4 in enhancing fibroblast proliferation and collagen synthesis. J. Immunol. 152, 3606–3614 (1994).
  CAS PubMed Google Scholar
• Doucet, C. et al. Interleukin (IL) 4 and IL-13 act on human lung fibroblasts. Implication in asthma. J. Clin. Invest. 101, 2129–2139 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Tiggelman, A. M., Boers, W., Linthorst, C., Sala, M. & Chamuleau, R. A. Collagen synthesis by human liver (myo)fibroblasts in culture: evidence for a regulatory role of IL-1β, IL-4, TGF-β and IFN-γ. J. Hepatol. 23, 307–317 (1995).
  CAS PubMed Google Scholar
• Cheever, A. W. et al. Anti-IL-4 treatment of _Schistosoma mansoni_-infected mice inhibits development of T cells and non-B, non-T cells expressing TH2 cytokines while decreasing egg-induced hepatic fibrosis. J. Immunol. 153, 753–759 (1994).
  CAS PubMed Google Scholar
• Ong, C., Wong, C., Roberts, C. R., Teh, H. S. & Jirik, F. R. Anti-IL-4 treatment prevents dermal collagen deposition in the tight-skin mouse model of scleroderma. Eur. J. Immunol. 28, 2619–2629 (1998).
  Article CAS PubMed Google Scholar
• Le Moine, A. et al. Critical roles for IL-4, IL-5, and eosinophils in chronic skin allograft rejection. J. Clin. Invest. 103, 1659–1667 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Zurawski, S. M., Vega, F. Jr, Huyghe, B. & Zurawski, G. Receptors for interleukin-13 and interleukin-4 are complex and share a novel component that functions in signal transduction. EMBO J. 12, 2663–2670 (1993).
  Article CAS PubMed PubMed Central Google Scholar
• McKenzie, G. J. et al. Impaired development of TH2 cells in IL-13-deficient mice. Immunity 9, 423–432 (1998).
  Article CAS PubMed Google Scholar
• Zhu, Z. et al. Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production. J. Clin. Invest. 103, 779–788 (1999). The first report to show the potent pro-fibrotic activity of IL-13 when overexpressed in the lung.
  Article CAS PubMed PubMed Central Google Scholar
• Donaldson, D. D. et al. The murine IL-13 receptor α2: molecular cloning, characterization, and comparison with murine IL-13 receptor α1. J. Immunol. 161, 2317–2324 (1998).
  CAS PubMed Google Scholar
• Chiaramonte, M. G., Donaldson, D. D., Cheever, A. W. & Wynn, T. A. An IL-13 inhibitor blocks the development of hepatic fibrosis during a T-helper type 2-dominated inflammatory response. J. Clin. Invest. 104, 777–785 (1999). The first experimental study to show that an IL-13 inhibitor can block the development of fibrosis.
  Article CAS PubMed PubMed Central Google Scholar
• Blease, K. et al. Therapeutic effect of IL-13 immunoneutralization during chronic experimental fungal asthma. J. Immunol. 166, 5219–5224 (2001).
  Article CAS PubMed Google Scholar
• Kumar, R. K. et al. Role of interleukin-13 in eosinophil accumulation and airway remodelling in a mouse model of chronic asthma. Clin. Exp. Allergy 32, 1104–1111 (2002).
  Article CAS PubMed Google Scholar
• Chiaramonte, M. G., Cheever, A. W., Malley, J. D., Donaldson, D. D. & Wynn, T. A. Studies of murine schistosomiasis reveal interleukin-13 blockade as a treatment for established and progressive liver fibrosis. Hepatology 34, 273–282 (2001).
  Article CAS PubMed Google Scholar
• Fallon, P. G., Richardson, E. J., McKenzie, G. J. & McKenzie, A. N. Schistosome infection of transgenic mice defines distinct and contrasting pathogenic roles for IL-4 and IL-13: IL-13 is a profibrotic agent. J. Immunol. 164, 2585–2591 (2000).
  Article CAS PubMed Google Scholar
• Belperio, J. A. et al. Interaction of IL-13 and C10 in the pathogenesis of bleomycin-induced pulmonary fibrosis. Am. J. Respir. Cell Mol. Biol. 27, 419–427 (2002).
  Article CAS PubMed Google Scholar
• Rankin, J. A. et al. Phenotypic and physiologic characterization of transgenic mice expressing interleukin 4 in the lung: lymphocytic and eosinophilic inflammation without airway hyperreactivity. Proc. Natl Acad. Sci. USA 93, 7821–7825 (1996).
  Article CAS PubMed PubMed Central Google Scholar
• Murata, T., Husain, S. R., Mohri, H. & Puri, R. K. Two different IL-13 receptor chains are expressed in normal human skin fibroblasts, and IL-4 and IL-13 mediate signal transduction through a common pathway. Int. Immunol. 10, 1103–1110 (1998).
  Article CAS PubMed Google Scholar
• Oriente, A. et al. Interleukin-13 modulates collagen homeostasis in human skin and keloid fibroblasts. J. Pharmacol. Exp. Ther. 292, 988–994 (2000).
  CAS PubMed Google Scholar
• Saito, A., Okazaki, H., Sugawara, I., Yamamoto, K. & Takizawa, H. Potential action of IL-4 and IL-13 as fibrogenic factors on lung fibroblasts in vitro. Int. Arch. Allergy Immunol. 132, 168–176 (2003).
  Article CAS PubMed Google Scholar
• Blease, K. et al. Stat6-deficient mice develop airway hyperresponsiveness and peribronchial fibrosis during chronic fungal asthma. Am. J. Pathol. 160, 481–490 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Webb, D. C. et al. Integrated signals between IL-13, IL-4, and IL-5 regulate airways hyperreactivity. J. Immunol. 165, 108–113 (2000).
  Article CAS PubMed Google Scholar
• Walter, D. M. et al. Critical role for IL-13 in the development of allergen-induced airway hyperreactivity. J. Immunol. 167, 4668–4675 (2001).
  Article CAS PubMed Google Scholar
• Webb, D. C. et al. Antigen-specific production of interleukin (IL)-13 and IL-5 cooperate to mediate IL-4Rα-independent airway hyperreactivity. Eur. J. Immunol. 33, 3377–3385 (2003).
  Article CAS PubMed Google Scholar
• Gharaee-Kermani, M. & Phan, S. H. Lung interleukin-5 expression in murine bleomycin-induced pulmonary fibrosis. Am. J. Respir. Cell Mol. Biol. 16, 438–447 (1997).
  Article CAS PubMed Google Scholar
• Sher, A., Coffman, R. L., Heiny, S., Scott, P. & Cheever, A. W. Interleukin 5 is required for the blood and tissue eosinophilia but not granuloma formation induced by infection with Schistosoma mansoni. Proc. Natl Acad. Sci. USA 87, 61–64 (1990).
  Article CAS PubMed PubMed Central Google Scholar
• Hao, H., Cohen, D. A., Jennings, C. D., Bryson, J. S. & Kaplan, A. M. Bleomycin-induced pulmonary fibrosis is independent of eosinophils. J. Leukoc. Biol. 68, 515–521 (2000).
  CAS PubMed Google Scholar
• Gharaee-Kermani, M. et al. The role of IL-5 in bleomycin-induced pulmonary fibrosis. J. Leukoc. Biol. 64, 657–666 (1998).
  Article CAS PubMed Google Scholar
• Blyth, D. I., Wharton, T. F., Pedrick, M. S., Savage, T. J. & Sanjar, S. Airway subepithelial fibrosis in a murine model of atopic asthma: suppression by dexamethasone or anti-interleukin-5 antibody. Am. J. Respir. Cell Mol. Biol. 23, 241–246 (2000).
  Article CAS PubMed Google Scholar
• Cho, J. Y. et al. Inhibition of airway remodeling in IL-5-deficient mice. J. Clin. Invest. 113, 551–560 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Huaux, F. et al. Eosinophils and T lymphocytes possess distinct roles in bleomycin-induced lung injury and fibrosis. J. Immunol. 171, 5470–5481 (2003).
  Article CAS PubMed Google Scholar
• Mattes, J. et al. Intrinsic defect in T cell production of interleukin (IL)-13 in the absence of both IL-5 and eotaxin precludes the development of eosinophilia and airways hyperreactivity in experimental asthma. J. Exp. Med. 195, 1433–1444 (2002). An important study identifying a link between IL-5, CCL11, eosinophils and IL-13.
  Article CAS PubMed PubMed Central Google Scholar
• Sato, M., Muragaki, Y., Saika, S., Roberts, A. B. & Ooshima, A. Targeted disruption of TGF-β1/Smad3 signaling protects against renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction. J. Clin. Invest. 112, 1486–1494 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Border, W. A. et al. Natural inhibitor of transforming growth factor-β protects against scarring in experimental kidney disease. Nature 360, 361–364 (1992). This study showed the effect of blocking TGF-β in the treatment of fibrotic kidney disease.
  Article CAS PubMed Google Scholar
• Clouthier, D. E., Comerford, S. A. & Hammer, R. E. Hepatic fibrosis, glomerulosclerosis, and a lipodystrophy-like syndrome in PEPCK–TGF-β1 transgenic mice. J. Clin. Invest. 100, 2697–2713 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Sime, P. J., Xing, Z., Graham, F. L., Csaky, K. G. & Gauldie, J. Adenovector-mediated gene transfer of active transforming growth factor-β1 induces prolonged severe fibrosis in rat lung. J. Clin. Invest. 100, 768–776 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Gorelik, L. & Flavell, R. A. Transforming growth factor-β in T-cell biology. Nature Rev. Immunol. 2, 46–53 (2002).
  Article CAS Google Scholar
• Munger, J. S. et al. The integrin-αvβ6 binds and activates latent TGF-β1: a mechanism for regulating pulmonary inflammation and fibrosis. Cell 96, 319–328 (1999).
  Article CAS PubMed Google Scholar
• Roberts, A. B., Russo, A., Felici, A. & Flanders, K. C. Smad3: a key player in pathogenetic mechanisms dependent on TGF-β. Ann. NY Acad. Sci. 995, 1–10 (2003).
  Article CAS PubMed Google Scholar
• Flanders, K. C. et al. Mice lacking Smad3 are protected against cutaneous injury induced by ionizing radiation. Am. J. Pathol. 160, 1057–1068 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Khalil, N., Corne, S., Whitman, C. & Yacyshyn, H. Plasmin regulates the activation of cell-associated latent TGF-β1 secreted by rat alveolar macrophages after in vivo bleomycin injury. Am. J. Respir. Cell Mol. Biol. 15, 252–259 (1996).
  Article CAS PubMed Google Scholar
• Ma, L. J. et al. Transforming growth factor-β-dependent and -independent pathways of induction of tubulointerstitial fibrosis in β6 −/− mice. Am. J. Pathol. 163, 1261–1273 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Ashcroft, G. S. et al. Mice lacking Smad3 show accelerated wound healing and an impaired local inflammatory response. Nature Cell Biol. 1, 260–266 (1999). The first study to implicate SMAD3 in specific pathways of tissue repair, indicating that SMAD3 might inhibit, rather than induce, the tissue-healing pathway.
  Article CAS PubMed Google Scholar
• Kaviratne, M. et al. IL-13 activates a mechanism of liver fibrosis that is completely TGF-β independent. J. Immunol. (in the press).
• Lee, C. G. et al. Interleukin-13 induces tissue fibrosis by selectively stimulating and activating transforming growth factor β1. J. Exp. Med. 194, 809–821 (2001). An important study that showed that IL-13 induces and activates latent TGF-β1 by an MMP9- and plasmin/serine protease-dependent mechanism.
  Article CAS PubMed PubMed Central Google Scholar
• Lanone, S. et al. Overlapping and enzyme-specific contributions of matrix metalloproteinases-9 and -12 in IL-13-induced inflammation and remodeling. J. Clin. Invest. 110, 463–474 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Nakao, A. et al. Blockade of transforming growth factor-β/Smad signaling in T cells by overexpression of Smad7 enhances antigen-induced airway inflammation and airway reactivity. J. Exp. Med. 192, 151–158 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Hansen, G. et al. CD4+ T helper cells engineered to produce latent TGF-β1 reverse allergen-induced airway hyperreactivity and inflammation. J. Clin. Invest. 105, 61–70 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Kitani, A. et al. Transforming growth factor (TGF)- β1-producing regulatory T cells induce Smad-mediated interleukin 10 secretion that facilitates coordinated immunoregulatory activity and amelioration of TGF-β1-mediated fibrosis. J. Exp. Med. 198, 1179–1188 (2003). This study showed that TGF-β1-producing regulatory T cells stimulate IL-10 production, which suppresses bleomycin-induced fibrosis.
  Article CAS PubMed PubMed Central Google Scholar
• Kulkarni, A. B. et al. Transforming growth factor β1 null mutation in mice causes excessive inflammatory response and early death. Proc. Natl Acad. Sci. USA 90, 770–774 (1993).
  Article CAS PubMed PubMed Central Google Scholar
• Smith, R. E. et al. Production and function of murine macrophage inflammatory protein-1α in bleomycin-induced lung injury. J. Immunol. 153, 4704–4712 (1994). The first report to establish an important role for CC-chemokines in fibrotic lung disease.
  CAS PubMed Google Scholar
• Smith, R. E. et al. A role for CC chemokines in fibrotic lung disease. J. Leukoc. Biol. 57, 782–787 (1995).
  Article CAS PubMed Google Scholar
• Lloyd, C. M. et al. RANTES and monocyte chemoattractant protein-1 (MCP-1) play an important role in the inflammatory phase of crescentic nephritis, but only MCP-1 is involved in crescent formation and interstitial fibrosis. J. Exp. Med. 185, 1371–1380 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Belperio, J. A. et al. Critical role for the chemokine MCP-1/CCR2 in the pathogenesis of bronchiolitis obliterans syndrome. J. Clin. Invest. 108, 547–556 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Tokuda, A. et al. Pivotal role of CCR1-positive leukocytes in bleomycin-induced lung fibrosis in mice. J. Immunol. 164, 2745–2751 (2000).
  Article CAS PubMed Google Scholar
• Blease, K. et al. Airway remodeling is absent in CCR1 −/− mice during chronic fungal allergic airway disease. J. Immunol. 165, 1564–1572 (2000).
  Article CAS PubMed Google Scholar
• Anders, H. J. et al. A chemokine receptor CCR-1 antagonist reduces renal fibrosis after unilateral ureter ligation. J. Clin. Invest. 109, 251–259 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Moore, B. B. et al. Protection from pulmonary fibrosis in the absence of CCR2 signaling. J. Immunol. 167, 4368–4377 (2001).
  Article CAS PubMed Google Scholar
• Zhu, Z. et al. IL-13-induced chemokine responses in the lung: role of CCR2 in the pathogenesis of IL-13-induced inflammation and remodeling. J. Immunol. 168, 2953–2962 (2002).
  Article CAS PubMed Google Scholar
• Gao, J. L. et al. Impaired host defense, hematopoiesis, granulomatous inflammation and type 1/type 2 cytokine balance in mice lacking CC chemokine receptor 1. J. Exp. Med. 185, 1959–1968 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Ma, B. et al. The C10/CCL6 chemokine and CCR1 play critical roles in the pathogenesis of IL-13-induced inflammation and remodeling. J. Immunol. 172, 1872–1881 (2004).
  Article CAS PubMed Google Scholar
• Gordon, S. Alternative activation of macrophages. Nature Rev. Immunol. 3, 23–35 (2003).
  Article CAS Google Scholar
• Munder, M., Eichmann, K. & Modolell, M. Alternative metabolic states in murine macrophages reflected by the nitric oxide synthase/arginase balance: competitive regulation by CD4+ T cells correlates with TH1/TH2 phenotype. J. Immunol. 160, 5347–5354 (1998).
  CAS PubMed Google Scholar
• Munder, M. et al. TH1/TH2-regulated expression of arginase isoforms in murine macrophages and dendritic cells. J. Immunol. 163, 3771–3777 (1999).
  CAS PubMed Google Scholar
• Witte, M. B., Barbul, A., Schick, M. A., Vogt, N. & Becker, H. D. Upregulation of arginase expression in wound-derived fibroblasts. J. Surg. Res. 105, 35–42 (2002).
  Article CAS PubMed Google Scholar
• Zimmermann, N. et al. Dissection of experimental asthma with DNA microarray analysis identifies arginase in asthma pathogenesis. J. Clin. Invest. 111, 1863–1874 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Hogaboam, C. M. et al. Collagen deposition in a non-fibrotic lung granuloma model after nitric oxide inhibition. Am. J. Pathol. 153, 1861–1872 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Numaguchi, K. et al. Chronic inhibition of nitric oxide synthesis causes coronary microvascular remodeling in rats. Hypertension 26, 957–962 (1995).
  Article CAS PubMed Google Scholar
• Moore, K. W., de Waal Malefyt, R., Coffman, R. L. & O'Garra, A. Interleukin-10 and the interleukin-10 receptor. Annu. Rev. Immunol. 19, 683–765 (2001).
  Article CAS PubMed Google Scholar
• Thompson, K. et al. Interleukin-10 expression and function in experimental murine liver inflammation and fibrosis. Hepatology 28, 1597–1606 (1998).
  Article CAS PubMed Google Scholar
• Louis, H. et al. Interleukin-10 controls neutrophilic infiltration, hepatocyte proliferation, and liver fibrosis induced by carbon tetrachloride in mice. Hepatology 28, 1607–1615 (1998).
  Article CAS PubMed Google Scholar
• Arai, T. et al. Introduction of the interleukin-10 gene into mice inhibited bleomycin-induced lung injury in vivo. Am. J. Physiol. Lung Cell. Mol. Physiol. 278, L914–L922 (2000).
  Article CAS PubMed Google Scholar
• Demols, A. et al. Endogenous interleukin-10 modulates fibrosis and regeneration in experimental chronic pancreatitis. Am. J. Physiol. Gastrointest. Liver Physiol. 282, G1105–G1112 (2002).
  Article CAS PubMed Google Scholar
• Wangoo, A., Laban, C., Cook, H. T., Glenville, B. & Shaw, R. J. Interleukin-10- and corticosteroid-induced reduction in type I procollagen in a human ex vivo scar culture. Int. J. Exp. Pathol. 78, 33–41 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Wang, S. C., Ohata, M., Schrum, L., Rippe, R. A. & Tsukamoto, H. Expression of interleukin-10 by in vitro and in vivo activated hepatic stellate cells. J. Biol. Chem. 273, 302–308 (1998).
  Article CAS PubMed Google Scholar
• Nelson, D. R. et al. Long-term interleukin 10 therapy in chronic hepatitis C patients has a proviral and anti-inflammatory effect. Hepatology 38, 859–868 (2003).
  Article CAS PubMed Google Scholar
• Wynn, T. A. et al. IL-10 regulates liver pathology in acute murine Schistosomiasis mansoni but is not required for immune down-modulation of chronic disease. J. Immunol. 160, 4473–4480 (1998).
  CAS PubMed Google Scholar
• Hesse, M. et al. The pathogenesis of schistosomiasis is controlled by cooperating IL-10-producing innate effector and regulatory T cells. J. Immunol. 172, 3157–3166 (2004).
  Article CAS PubMed Google Scholar
• Lee, C. G. et al. Transgenic overexpression of interleukin (IL)-10 in the lung causes mucus metaplasia, tissue inflammation, and airway remodeling via IL-13-dependent and -independent pathways. J. Biol. Chem. 277, 35466–35474 (2002).
  Article CAS PubMed Google Scholar
• Taube, C. et al. The role of IL-13 in established allergic airway disease. J. Immunol. 169, 6482–6489 (2002).
  Article CAS PubMed Google Scholar
• Mattes, J. et al. IL-13 induces airways hyperreactivity independently of the IL-4R α-chain in the allergic lung. J. Immunol. 167, 1683–1692 (2001).
  Article CAS PubMed Google Scholar
• Feng, N. et al. The interleukin-4/interleukin-13 receptor of human synovial fibroblasts: overexpression of the nonsignaling interleukin-13 receptor α2. Lab. Invest. 78, 591–602 (1998).
  CAS PubMed Google Scholar
• Wood, N. et al. Enhanced interleukin (IL)-13 responses in mice lacking IL-13 receptor α2. J. Exp. Med. 197, 703–709 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Chiaramonte, M. G. et al. Regulation and function of the interleukin 13 receptor α2 during a T helper cell type 2-dominant immune response. J. Exp. Med. 197, 687–701 (2003). This study provides evidence that IL-13Rα2 functions as a decoy receptor for IL-13. The development of liver fibrosis was accelerated in S. mansoni -infected IL-13Rα2-deficient mice.
  Article CAS PubMed PubMed Central Google Scholar
• Mentink-Kane, M. M. et al. IL-13 receptor α2 down-modulates granulomatous inflammation and prolongs host survival in schistosomiasis. Proc. Natl Acad. Sci. USA 101, 586–590 (2004).
  Article CAS PubMed Google Scholar
• Zheng, T. et al. Cytokine regulation of IL-13Rα2 and IL-13Rα1 in vivo and in vitro. J. Allergy Clin. Immunol. 111, 720–728 (2003).
  Article CAS PubMed Google Scholar
• Jakubzick, C. et al. Impact of interleukin-13 responsiveness on the synthetic and proliferative properties of TH1- and TH2-type pulmonary granuloma fibroblasts. Am. J. Pathol. 162, 1475–1486 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Daines, M. O. & Hershey, G. K. A novel mechanism by which interferon-γ can regulate interleukin (IL)-13 responses. Evidence for intracellular stores of IL-13 receptor α-2 and their rapid mobilization by interferon-γ. J. Biol. Chem. 277, 10387–10393 (2002).
  Article CAS PubMed Google Scholar
• Wynn, T. A. et al. P-selectin suppresses hepatic inflammation and fibrosis in mice by regulating interferon-γ and the IL-13 decoy receptor. Hepatology 39, 676–687 (2004).
  Article CAS PubMed Google Scholar
• Clark, J. G., Dedon, T. F., Wayner, E. A. & Carter, W. G. Effects of interferon-γ on expression of cell surface receptors for collagen and deposition of newly synthesized collagen by cultured human lung fibroblasts. J. Clin. Invest. 83, 1505–1511 (1989).
  Article CAS PubMed PubMed Central Google Scholar
• Hansen, G., Berry, G., DeKruyff, R. H. & Umetsu, D. T. Allergen-specific TH1 cells fail to counterbalance TH2 cell-induced airway hyperreactivity but cause severe airway inflammation. J. Clin. Invest. 103, 175–183 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Randolph, D. A., Stephens, R., Carruthers, C. J. & Chaplin, D. D. Cooperation between TH1 and TH2 cells in a murine model of eosinophilic airway inflammation. J. Clin. Invest. 104, 1021–1029 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Ford, J. G. et al. IL-13 and IFN-γ: interactions in lung inflammation. J. Immunol. 167, 1769–1777 (2001).
  Article CAS PubMed Google Scholar
• Castro, M., Chaplin, D. D., Walter, M. J. & Holtzman, M. J. Could asthma be worsened by stimulating the T-helper type 1 immune response? Am. J. Respir. Cell Mol. Biol. 22, 143–146 (2000).
  Article CAS PubMed Google Scholar
• Wills-Karp, M. et al. Interleukin-13: central mediator of allergic asthma. Science 282, 2258–2261 (1998).
  Article CAS PubMed Google Scholar
• Grunig, G. et al. Requirement for IL-13 independently of IL-4 in experimental asthma. Science 282, 2261–2263 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Marth, T., Strober, W., Seder, R. A. & Kelsall, B. L. Regulation of transforming growth factor-β production by interleukin-12. Eur. J. Immunol. 27, 1213–1220 (1997).
  Article CAS PubMed Google Scholar
• Nelson, D. R., Lauwers, G. Y., Lau, J. Y. & Davis, G. L. Interleukin 10 treatment reduces fibrosis in patients with chronic hepatitis C: a pilot trial of interferon nonresponders. Gastroenterology 118, 655–660 (2000).
  Article CAS PubMed Google Scholar
• Kaufman, J., Sime, P. J. & Phipps, R. P. Expression of CD154 (CD40 ligand) by human lung fibroblasts: differential regulation by IFN-γ and IL-13, and implications for fibrosis. J. Immunol. 172, 1862–1871 (2004).
  Article CAS PubMed Google Scholar
• Adawi, A. et al. Blockade of CD40–CD40 ligand interactions protects against radiation-induced pulmonary inflammation and fibrosis. Clin. Immunol. Immunopathol. 89, 222–230 (1998).
  Article CAS PubMed Google Scholar
• Katsuma, S. et al. Molecular monitoring of bleomycin-induced pulmonary fibrosis by cDNA microarray-based gene expression profiling. Biochem. Biophys. Res. Commun. 288, 747–751 (2001).
  Article CAS PubMed Google Scholar
• Kaminski, N. Microarray analysis of idiopathic pulmonary fibrosis. Am. J. Respir. Cell Mol. Biol. 29, S32–S36 (2003).
  Article CAS PubMed Google Scholar
• Anders, R. A. et al. cDNA microarray analysis of macroregenerative and dysplastic nodules in end-stage hepatitis C virus-induced cirrhosis. Am. J. Pathol. 162, 991–1000 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Abbas, A. K., Murphy, K. M. & Sher, A. Functional diversity of helper T lymphocytes. Nature 383, 787–793 (1996).
  Article CAS PubMed Google Scholar