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Goblet cell-derived resistin-like molecule beta augments CD4+ T cell production of IFN-gamma and infection-induced intestinal inflammation.
Nair, Meera G; Guild, Katherine J; Du, Yurong; Zaph, Colby; Yancopoulos, George D; Valenzuela, David M; Murphy, Andrew; Stevens, Sean; Karow, Margaret; Artis, David.
Affiliation
  • Nair MG; Department of Pathobiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
J Immunol ; 181(7): 4709-15, 2008 Oct 01.
Article in En | MEDLINE | ID: mdl-18802073
The secreted goblet cell-derived protein resistin-like molecule beta (RELMbeta) has been implicated in divergent functions, including a direct effector function against parasitic helminths and a pathogenic function in promoting inflammation in models of colitis and ileitis. However, whether RELMbeta influences CD4(+) T cell responses in the intestine is unknown. Using a natural model of intestinal inflammation induced by chronic infection with gastrointestinal helminth Trichuris muris, we identify dual functions for RELMbeta in augmenting CD4(+) Th1 cell responses and promoting infection-induced intestinal inflammation. Following exposure to low-dose Trichuris, wild-type C57BL/6 mice exhibit persistent infection associated with robust IFN-gamma production and intestinal inflammation. In contrast, infected RELMbeta(-/-) mice exhibited a significantly reduced expression of parasite-specific CD4(+) T cell-derived IFN-gamma and TNF-alpha and failed to develop Trichuris-induced intestinal inflammation. In in vitro T cell differentiation assays, recombinant RELMbeta activated macrophages to express MHC class II and secrete IL-12/23p40 and enhanced their ability to mediate Ag-specific IFN-gamma expression in CD4(+) T cells. Taken together, these data suggest that goblet cell-macrophage cross-talk, mediated in part by RELMbeta, can promote adaptive CD4(+) T cell responses and chronic inflammation following intestinal helminth infection.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Trichuriasis / CD4-Positive T-Lymphocytes / Interferon-gamma / Inflammation Mediators / Goblet Cells / Hormones, Ectopic / Intestinal Diseases, Parasitic Type of study: Prognostic_studies Limits: Animals Language: En Journal: J Immunol Year: 2008 Document type: Article Affiliation country: United States Country of publication: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Trichuriasis / CD4-Positive T-Lymphocytes / Interferon-gamma / Inflammation Mediators / Goblet Cells / Hormones, Ectopic / Intestinal Diseases, Parasitic Type of study: Prognostic_studies Limits: Animals Language: En Journal: J Immunol Year: 2008 Document type: Article Affiliation country: United States Country of publication: United States