Premium
A dual function for RELMβ in promoting T H 1 immune responses and infection‐induced intestinal inflammation
Author(s) -
Nair Meera G,
Guild Katherine J,
Du Yurong,
Stevens Sean,
Karow Margaret,
Artis David
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.852.3
Subject(s) - proinflammatory cytokine , inflammation , immunology , biology , immune system , secretion , immunity , context (archaeology) , interleukin 13 , interleukin 17 , interleukin 4 , endocrinology , paleontology
The secreted goblet cell‐derived protein Resistin‐like moleculeβ (RELMβ) has been implicated in divergent functions including immunity to intestinal infection and promotion of chemical‐induced colitis. However, the mechanisms through which RELMβ influences proinflammatory responses and adaptive immunity are undefined. To investigate the function of RELMβ in this context, we employed a model of chronic Trichuris infection characterized by RELMβ expression, IFNγ production and severe intestinal inflammation. In contrast to WT mice, RELMβ −/− mice failed to establish chronic infection, and parasite clearance was associated with decreased production of IFNγ and TNFα and reduced intestinal inflammation. Based on these findings, we hypothesized a role for RELMβ in promoting proinflammatory responses by influencing accessory cell function and/or through direct effects on CD4 T cells. While recombinant RELMβ did not directly affect CD4 T cells, rRELMβ treatment of macrophages induced MHC Class II expression, secretion of IL‐12 and TNFα , and augmented their ability to promote antigen‐specific T H 1 cell differentiation. Taken together, these data demonstrate a previously unidentified role for an intestinal goblet cell‐derived factor in the modulation of proinflammatory responses and adaptive immunity through direct effects on macrophages.