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

被引：240

作者：

Zaph, Colby ^{[1
]}

Du, Yurong ^{[1
]}

Saenz, Steven A. ^{[1
]}

Nair, Meera G. ^{[1
]}

Perrigoue, Jacqueline G. ^{[1
]}

Taylor, Betsy C. ^{[1
]}

Troy, Amy E. ^{[1
]}

Kobuley, Dmytro E. ^{[2
]}

Kastelein, Robert A. ^{[3
]}

Cua, Daniel J. ^{[3
]}

Yu, Yimin ^{[2
]}

Artis, David ^{[1
]}

机构：

[1] Univ Penn, Dept Pathobiol, Philadelphia, PA 19104 USA

[2] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA

[3] Schering Plough Biopharma, Discovery Res, Palo Alto, CA 94304 USA

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2008年 / 205卷 / 10期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1084/jem.20080720

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：2191 / 2198

页数：8

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