T helper 1-inducing property of IL-27/WSX-1 signaling is required for the induction of experimental colitis.
BACKGROUND
WSX-1, a component of the interleukin (IL)-27 receptor, is a novel class I cytokine receptor with homology to the IL-12 receptor beta2 chain. Initially, WSX-1 signaling was reported to play an important role in the promotion of T helper-1 responses, but recent reports have revealed an anti-inflammatory property in WSX-1 signaling. In the present study, we investigated the role of IL-27/WSX-1 signaling in a murine colitis model, dextran sulfate sodium (DSS) colitis, by using WSX-1 knockout (KO) mice.


METHODS
First, we observed whether WSX-1 KO mice developed colitis spontaneously. Second, we induced DSS colitis in WSX-1 KO and wild-type (WT) mice.


RESULTS
WSX-1 KO mice were observed not to develop colitis spontaneously. The severity of DSS colitis was decreased in WSX-1 KO mice in comparison with WT mice in association with a reduced production of interferon-gamma, IL-6, and tumor necrosis factor-alpha by lamina propria mononuclear cells from WSX-1 KO mice and the absence of T-bet expression in the colon from WSX-1 KO mice.


CONCLUSIONS
This study revealed the inflammatory property of IL-27/WSX-1 signaling in intestinal inflammation. As a result, IL-27/WSX-1 signal pathway may thus be a promising candidate for the therapeutic intervention of human inflammatory bowel diseases such as Crohn's disease and ulcerative colitis.
Honda
Kuniomi
K
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Nakamura
Kazuhiko
K
Matsui
Noriaki
N
Takahashi
Makoto
M
Kitamura
Yousuke
Y
Mizutani
Takahiro
T
Harada
Naohiko
N
Nawata
Hajime
H
Hamano
Shinjiro
S
Yoshida
Hiroki
H
D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000503:physiopathology*; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D015850:Interleukin-6 / Q000097:blood; D007378:Interleukins / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020825:T-Box Domain Proteins; D018417:Th1 Cells / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D000098815:T-bet Transcription Factor
C486767:Il27 protein, mouse; D015850:Interleukin-6; D007378:Interleukins; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D016264:Dextran Sulfate