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J Exp Med. 2008 Sep 29;205(10):2191-8. doi: 10.1084/jem.20080720. Epub 2008 Sep 1.

Commensal-dependent expression of IL-25 regulates the IL-23-IL-17 axis in the intestine.

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  • 1Department of Pathobiology, University of Pennsylvania, Philadelphia, PA 19104, USA.

Abstract

Alterations in the composition of intestinal commensal bacteria are associated with enhanced susceptibility to multiple inflammatory diseases, including those conditions associated with interleukin (IL)-17-producing CD4(+) T helper (Th17) cells. However, the relationship between commensal bacteria and the expression of proinflammatory cytokines remains unclear. Using germ-free mice, we show that the frequency of Th17 cells in the large intestine is significantly elevated in the absence of commensal bacteria. Commensal-dependent expression of the IL-17 family member IL-25 (IL-17E) by intestinal epithelial cells limits the expansion of Th17 cells in the intestine by inhibiting expression of macrophage-derived IL-23. We propose that acquisition of, or alterations in, commensal bacteria influences intestinal immune homeostasis via direct regulation of the IL-25-IL-23-IL-17 axis.

PMID:
18762568
[PubMed - indexed for MEDLINE]
PMCID:
PMC2556798
Free PMC Article

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