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

被引：238

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

共 30 条

[1] Interleukin 25 promotes the initiation of proallergic type 2 responses
Angkasekwinai, Pornpimon
Park, Heon
Wang, Yui-Hsi
Wang, Yi-Hong
Chang, Seon Hee
Corry, David B.
Liu, Yong-Jun
Zhu, Zhou
Dong, Chen
[J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (07) : 1509 - 1517
[2] Toll-like receptor 4 signaling by intestinal microbes influences susceptibility to food allergy
Bashir, MEH
Louie, S
Shi, HN
Nagler-Anderson, C
[J]. JOURNAL OF IMMUNOLOGY, 2004, 172 (11) : 6978 - 6987
[3] Interleukin 27 limits autoimmune encephalomyelitis by suppressing the development of interleukin 17-producing T cells
Batten, Marcel
Li, Ji
Yi, Sothy
Kljavin, Noelyn M.
Danilenko, Dimitry M.
Lucas, Sophie
Lee, James
de Sauvage, Frederic J.
Ghilardi, Nico
[J]. NATURE IMMUNOLOGY, 2006, 7 (09) : 929 - 936
[4] Constitutive p40 promoter activation and IL-23 production in the terminal ileum mediated by dendritic cells
Becker, C
Wirtz, S
Blessing, M
Pirhonen, J
Strand, D
Bechthold, O
Frick, J
Galle, PR
Autenrieth, I
Neurath, MF
[J]. JOURNAL OF CLINICAL INVESTIGATION, 2003, 112 (05) : 693 - 706
[5] TH-17 cells in the circle of immunity and autoimmunity
Bettelli, Estelle
Oukka, Mohamed
Kuchroo, Vijay K.
[J]. NATURE IMMUNOLOGY, 2007, 8 (04) : 345 - 350
[6] Cutting edge: Bacterial modulation of epithelial signaling via changes in neddylation of cullin-1
Collier-Hyams, LS
Sloane, V
Batten, BC
Neish, AS
[J]. JOURNAL OF IMMUNOLOGY, 2005, 175 (07) : 4194 - 4198
[7] IL-25 induces IL-4 IL-5, and IL-13 and Th2-associated pathologies in vivo
Fort, MM
Cheung, J
Yen, D
Li, J
Zurawski, SM
Lo, S
Menon, S
Clifford, T
Hunte, B
Lesley, R
Muchamuel, T
Hurst, SD
Zurawski, G
Leach, MW
Gorman, DM
Rennick, DM
[J]. IMMUNITY, 2001, 15 (06) : 985 - 995
[8] Commensal host-bacterial relationships in the gut
Hooper, LV
Gordon, JI
[J]. SCIENCE, 2001, 292 (5519) : 1115 - 1118
[9] Mast cells produce interleukin-25 upon FcεRI-mediated activation
Ikeda, K
Nakajima, H
Suzuki, K
Kagami, SI
Hirose, K
Suto, A
Saito, Y
Iwamoto, I
[J]. BLOOD, 2003, 101 (09) : 3594 - 3596
[10] The orphan nuclear receptor RORγt directs the differentiation program of proinflammatory IL-17+ T helper cells
Ivanov, Ivaylo I.
McKenzie, Brent S.
Zhou, Liang
Tadokoro, Carlos E.
Lepelley, Alice
Lafaille, Juan J.
Cua, Daniel J.
Littman, Dan R.
[J]. CELL, 2006, 126 (06) : 1121 - 1133

← 1 2 3 →