Macrophages in chronic type 2 inflammation have a novel phenotype characterized by the abundant expression of Ym1 and Fizz1 that can be partly replicated in vitro - PubMed (original) (raw)
Macrophages in chronic type 2 inflammation have a novel phenotype characterized by the abundant expression of Ym1 and Fizz1 that can be partly replicated in vitro
Meera G Nair et al. Immunol Lett. 2003.
Abstract
Using a murine model of nematode infection, we have discovered macrophages that display a novel phenotype that may be characteristic of macrophages in chronic type 2 inflammation. These nematode-elicited macrophages (NeMphi) are characterized by two unique features: the ability to actively suppress proliferation of a broad range of cell types and the high level expression of two novel macrophage genes, Ym1 and Fizz1. NeMphi also show some similarities with in vitro-derived 'alternatively activated macrophages' such as the downregulation of inflammatory cytokines. We therefore investigated how much of the phenotype discovered in vivo could be replicated by activation with Th2 cytokines in vitro. Fizz1 and Ym1 were upregulated by IL-4 and IL-13 in vitro but at a considerably lower level than in NeMphi. In vitro treatment with IL-4 could also partly replicate the ability of NeMphi to block cellular proliferation. As well as the quantitative differences in gene expression and suppressive phenotype, we also observed phenotypic differences in the cell morphology between macrophages activated in vivo and in vitro. Although this study illustrated that macrophages activated in chronic inflammation have distinct features that cannot be readily reproduced in vitro it also demonstrated that some features of the complex NeMphi phenotype can be replicated by treatment of cultured macrophages with Th2 cytokines. In future, we hope to use in vitro analysis to help define the pathways that lead to this distinctive in vivo macrophage phenotype.
Similar articles
- Alternatively activated macrophages elicited by helminth infection can be reprogrammed to enable microbial killing.
Mylonas KJ, Nair MG, Prieto-Lafuente L, Paape D, Allen JE. Mylonas KJ, et al. J Immunol. 2009 Mar 1;182(5):3084-94. doi: 10.4049/jimmunol.0803463. J Immunol. 2009. PMID: 19234205 - Chitinase and Fizz family members are a generalized feature of nematode infection with selective upregulation of Ym1 and Fizz1 by antigen-presenting cells.
Nair MG, Gallagher IJ, Taylor MD, Loke P, Coulson PS, Wilson RA, Maizels RM, Allen JE. Nair MG, et al. Infect Immun. 2005 Jan;73(1):385-94. doi: 10.1128/IAI.73.1.385-394.2005. Infect Immun. 2005. PMID: 15618176 Free PMC article. - IL-4 dependent alternatively-activated macrophages have a distinctive in vivo gene expression phenotype.
Loke P, Nair MG, Parkinson J, Guiliano D, Blaxter M, Allen JE. Loke P, et al. BMC Immunol. 2002 Jul 4;3:7. doi: 10.1186/1471-2172-3-7. BMC Immunol. 2002. PMID: 12098359 Free PMC article. - Interleukin-4- and interleukin-13-mediated alternatively activated macrophages: roles in homeostasis and disease.
Van Dyken SJ, Locksley RM. Van Dyken SJ, et al. Annu Rev Immunol. 2013;31:317-43. doi: 10.1146/annurev-immunol-032712-095906. Epub 2013 Jan 3. Annu Rev Immunol. 2013. PMID: 23298208 Free PMC article. Review. - An update on Ym1 and its immunoregulatory role in diseases.
Kang Q, Li L, Pang Y, Zhu W, Meng L. Kang Q, et al. Front Immunol. 2022 Jul 28;13:891220. doi: 10.3389/fimmu.2022.891220. eCollection 2022. Front Immunol. 2022. PMID: 35967383 Free PMC article. Review.
Cited by
- Contribution of alternatively activated macrophages to allergic lung inflammation: a tale of mice and men.
Dasgupta P, Keegan AD. Dasgupta P, et al. J Innate Immun. 2012;4(5-6):478-88. doi: 10.1159/000336025. Epub 2012 Mar 21. J Innate Immun. 2012. PMID: 22440980 Free PMC article. - Immunopathogenesis of lymphatic filarial disease.
Babu S, Nutman TB. Babu S, et al. Semin Immunopathol. 2012 Nov;34(6):847-61. doi: 10.1007/s00281-012-0346-4. Epub 2012 Oct 3. Semin Immunopathol. 2012. PMID: 23053393 Free PMC article. Review. - Proteomic Analysis Provides Insights Into the Therapeutic Effect of GU-BEN-FANG-XIAO Decoction on a Persistent Asthmatic Mouse Model.
Liu LW, Xing QQ, Zhao X, Tan M, Lu Y, Dong YM, Dai C, Zhang Y. Liu LW, et al. Front Pharmacol. 2019 May 7;10:441. doi: 10.3389/fphar.2019.00441. eCollection 2019. Front Pharmacol. 2019. PMID: 31133848 Free PMC article. - Diabetic Wounds Exhibit Decreased Ym1 and Arginase Expression with Increased Expression of IL-17 and IL-20.
Finley PJ, DeClue CE, Sell SA, DeBartolo JM, Shornick LP. Finley PJ, et al. Adv Wound Care (New Rochelle). 2016 Nov 1;5(11):486-494. doi: 10.1089/wound.2015.0676. Adv Wound Care (New Rochelle). 2016. PMID: 27867753 Free PMC article. - Thalidomide inhibits alternative activation of macrophages in vivo and in vitro: a potential mechanism of anti-asthmatic effect of thalidomide.
Lee HS, Kwon HS, Park DE, Woo YD, Kim HY, Kim HR, Cho SH, Min KU, Kang HR, Chang YS. Lee HS, et al. PLoS One. 2015 Apr 23;10(4):e0123094. doi: 10.1371/journal.pone.0123094. eCollection 2015. PLoS One. 2015. PMID: 25905462 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Research Materials
Miscellaneous