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

Colby Zaph, Yurong Du, Steven A. Saenz, Meera G. Nair, Jacqueline G. Perrigoue, Betsy C. Taylor, Amy E. Troy, Dmytro E. Kobuley, Robert A. Kastelein, Daniel J. Cua, Yimin Yu, David Artis

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218 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2191-2198
Number of pages8
JournalJournal of Experimental Medicine
Volume205
Issue number10
DOIs
Publication statusPublished - 29 Sep 2008
Externally publishedYes

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