Development of colitis in signal transducers and activators of transcription 6-deficient T-cell receptor α-deficient mice -: A potential role of signal transducers and activators of transcription 6-independent interleukin-4 signaling for the generation of Th2-biased pathological CD4+ ββT cells

被引:15
作者
Okuda, Y
Takahashi, I
Kim, JK
Ohta, N
Iwatani, K
Iijima, H
Kai, Y
Tamagawa, H
Hiroi, T
Kweon, MN
Kawano, S
Takeda, K
Akira, S
Sasaki, Y
Hori, M
Kiyono, H
机构
[1] Hiroshima Univ, Grad Sch Biomed Sci, Dept Prevent Dent & Host Def, Hiroshima 7348553, Japan
[2] Osaka Univ, Fac Med, Microbial Dis Res Inst, Dept Mucsoal Immunol, Osaka, Japan
[3] Osaka Univ, Fac Med, Microbial Dis Res Inst, Dept Host Def, Osaka, Japan
[4] Osaka Univ, Fac Med, Sch Allied Hlth Sci, Dept Internal Med & Therapeut, Osaka, Japan
[5] Osaka Univ, Fac Med, Sch Allied Hlth Sci, Dept Clin Lab Sci, Osaka, Japan
[6] Univ Tokyo, Inst Med Sci, Div Mucosal Immunol, Dept Microbiol & Immunol, Tokyo, Japan
关键词
D O I
10.1016/S0002-9440(10)63817-5
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Forbidden CD4(+)betabeta T cells, which produce interleukin (IL)-4 predominantly, are a pathological subset in the development of colitis in T-cell receptor alpha chain (TCRalpha)-deficient mice. Stimulation of naive CD4(+) T cells with H,4 induces Th2 development via the activation of signal transducers and activators of transcription (STAT) 6. in the present study, we had found that IL-4 enhanced the expression of STAT6 in CD4(+)betabeta T cells isolated from TCRalpha(-/-) mice with colitis, suggesting that the IL-4 signal in the CD4(+)betabeta T cells is mediated by STAT6. To further investigate the role of STAT6 in the development of colitis induced by TCRalpha deficiency, we generated double-deficient mice by crossing TCRalpha(-/-) mice and STAT6(-/-) mice. Surprisingly, STAT6 deficiency did not result in decreased severity of colitis in TCRa-/- mice. STAT6-deficient CD4(+)betabeta T cells produced IL-4 and intraperitoneal injection of anti-IL-4 monoclonal antibody in the nondiseased TCRalpha(-/-) and STAT6 double-deficient mice prevented the colitis formation, thus indicating that the cells differentiated into the Th2 phenotype have the ability to mediate the development of the colitis in the absence of STAT6.
引用
收藏
页码:263 / 271
页数:9
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