Small intestinal eosinophils regulate Th17 cells by producing IL-1 receptor antagonist

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Eosinophils play proinflammatory roles in helminth infections and allergic diseases. Under steady-state conditions, eosinophils are abundantly found in the small intestinal lamina propria, but their physiological function is largely unexplored. In this study, we found that small intestinal eosinophils down-regulate Th17 cells. Th17 cells in the small intestine were markedly increased in the Delta dblGATA-1 mice lacking eosinophils, and an inverse correlation was observed between the number of eosinophils and that of Th17 cells in the small intestine of wild-type mice. In addition, small intestinal eosinophils suppressed the in vitro differentiation of Th17 cells, as well as IL-17 production by small intestinal CD4(+) T cells. Unlike other small intestinal immune cells or circulating eosinophils, we found that small intestinal eosinophils have a unique ability to constitutively secrete high levels of IL-1 receptor antagonist (IL-1Ra), a natural inhibitor of IL-1 beta. Moreover, small intestinal eosinophils isolated from IL-1Ra-deficient mice failed to suppress Th17 cells. Collectively, our results demonstrate that small intestinal eosinophils play a pivotal role in the maintenance of intestinal homeostasis by regulating Th17 cells via production of IL-1Ra.
Publisher
ROCKEFELLER UNIV PRESS
Issue Date
2016-04
Language
English
Article Type
Article
Keywords

COLONY-STIMULATING FACTOR; EPITHELIAL-CELLS; T(H)17 CELLS; GM-CSF; GASTROINTESTINAL-TRACT; AIRWAY INFLAMMATION; IMMUNE HOMEOSTASIS; T-CELLS; IN-VIVO; MICE

Citation

JOURNAL OF EXPERIMENTAL MEDICINE, v.213, no.4, pp.555 - 567

ISSN
0022-1007
DOI
10.1084/jem.20141388
URI
http://hdl.handle.net/10203/240765
Appears in Collection
MSE-Journal Papers(저널논문)
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