Commensal-dependent Expression of IL-25 Regulates the IL-23-IL-17 Axis in the Intestine

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2008 Sep 3

PMID 18762568

Citations 139

Authors

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

Affiliations

Soon will be listed here.

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.

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