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

• Published in: The Journal of experimental medicine Vol. 205; no. 10; pp. 2191 - 2198
• Main Authors: Zaph, Colby, Du, Yurong, Saenz, Steven A, Nair, Meera G, Perrigoue, Jacqueline G, Taylor, Betsy C, Troy, Amy E, Kobuley, Dmytro E, Kastelein, Robert A, Cua, Daniel J, Yu, Yimin, Artis, David
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 29.09.2008
• Subjects: Animals; Brief Definitive Reports; Epithelial Cells - immunology; Epithelial Cells - microbiology; Germ-Free Life; Homeostasis; Interleukin-17 - genetics; Interleukin-17 - metabolism; Interleukin-23 - genetics; Interleukin-23 - metabolism; Interleukins - genetics; Interleukins - metabolism; Intestinal Mucosa - cytology; Intestinal Mucosa - immunology; Intestines - anatomy & histology; Intestines - immunology; Intestines - microbiology; Macrophages - immunology; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; STAT6 Transcription Factor - genetics; STAT6 Transcription Factor - metabolism; Symbiosis; T-Lymphocyte Subsets - immunology; T-Lymphocytes, Helper-Inducer - immunology
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.20080720

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.