Commensal-dependent expression of IL-25 regulates the IL-23-IL-17 axis in the intestine.
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.
Zaph
Colby
C
Department of Pathobiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Du
Yurong
Y
Saenz
Steven A
SA
Nair
Meera G
MG
Perrigoue
Jacqueline G
JG
Taylor
Betsy C
BC
Troy
Amy E
AE
Kobuley
Dmytro E
DE
Kastelein
Robert A
RA
Cua
Daniel J
DJ
Yu
Yimin
Y
Artis
David
D