Goblet cell-derived resistin-like molecule beta augments CD4+ T cell production of IFN-gamma and infection-induced intestinal inflammation

• Published in: The Journal of immunology (1950) Vol. 181; no. 7; pp. 4709 - 4715
• Main Authors: Nair, Meera G, Guild, Katherine J, Du, Yurong, Zaph, Colby, Yancopoulos, George D, Valenzuela, David M, Murphy, Andrew, Stevens, Sean, Karow, Margaret, Artis, David
• Format: Journal Article
• Language: English
• Published: United States 01.10.2008
• Subjects: Acute Disease; Adjuvants, Immunologic - physiology; Animals; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Cell Communication - immunology; Chronic Disease; Goblet Cells - immunology; Goblet Cells - metabolism; Hormones, Ectopic - genetics; Hormones, Ectopic - physiology; Inflammation Mediators - physiology; Interferon-gamma - biosynthesis; Intestinal Diseases, Parasitic - immunology; Intestinal Diseases, Parasitic - metabolism; Intestinal Diseases, Parasitic - pathology; Macrophages - immunology; Macrophages - pathology; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Resistin - genetics; Resistin - physiology; Trichuriasis - immunology; Trichuriasis - metabolism; Trichuriasis - pathology; Trichuris - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.181.7.4709

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.