First Author | Sugawara R | Year | 2016 |
Journal | J Exp Med | Volume | 213 |
Issue | 4 | Pages | 555-67 |
PubMed ID | 26951334 | Mgi Jnum | J:233006 |
Mgi Id | MGI:5780604 | Doi | 10.1084/jem.20141388 |
Citation | Sugawara R, et al. (2016) Small intestinal eosinophils regulate Th17 cells by producing IL-1 receptor antagonist. J Exp Med 213(4):555-67 |
abstractText | 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 DeltadblGATA-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-1beta. 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. |