TY - JOUR
T1 - Goblet cell-derived resistin-like molecule β augments CD4+ T cell production of IFN-γ and infection-induced intestinal inflammation
AU - Nair, Meera G.
AU - Guild, Katherine J.
AU - Du, Yurong
AU - Zaph, Colby
AU - Yancopoulos, George D.
AU - Valenzuela, David M.
AU - Murphy, Andrew
AU - Stevens, Sean
AU - Karow, Margaret
AU - Artis, David
PY - 2008/10/1
Y1 - 2008/10/1
N2 - The secreted goblet cell-derived protein resistin-like molecule β (RELMβ) 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 RELMβ 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 RELMβ 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-γ production and intestinal inflammation. In contrast, infected RELMβ-/- mice exhibited a significantly reduced expression of parasite-specific CD4+ T cell-derived IFN-γ and TNF-α and failed to develop Trichuris-induced intestinal inflammation. In in vitro T cell differentiation assays, recombinant RELMβ activated macrophages to express MHC class II and secrete IL-12/23p40 and enhanced their ability to mediate Ag-specific IFN-γexpression in CD4 + T cells. Taken together, these data suggest that goblet cell-macrophage cross-talk, mediated in part by RELMβ, can promote adaptive CD4+ T cell responses and chronic inflammation following intestinal helminth infection.
AB - The secreted goblet cell-derived protein resistin-like molecule β (RELMβ) 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 RELMβ 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 RELMβ 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-γ production and intestinal inflammation. In contrast, infected RELMβ-/- mice exhibited a significantly reduced expression of parasite-specific CD4+ T cell-derived IFN-γ and TNF-α and failed to develop Trichuris-induced intestinal inflammation. In in vitro T cell differentiation assays, recombinant RELMβ activated macrophages to express MHC class II and secrete IL-12/23p40 and enhanced their ability to mediate Ag-specific IFN-γexpression in CD4 + T cells. Taken together, these data suggest that goblet cell-macrophage cross-talk, mediated in part by RELMβ, can promote adaptive CD4+ T cell responses and chronic inflammation following intestinal helminth infection.
UR - http://www.scopus.com/inward/record.url?scp=58149286587&partnerID=8YFLogxK
M3 - Article
C2 - 18802073
AN - SCOPUS:58149286587
SN - 0022-1767
VL - 181
SP - 4709
EP - 4715
JO - Journal of Immunology
JF - Journal of Immunology
IS - 7
ER -