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
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
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DOI：
10.1016/s0002-9440(10)63817-5
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发表时间：
2003-01-01
影响因子：
6
通讯作者：
Kiyono, H
中科院分区：
文献类型：
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作者：
Okuda, Y;Takahashi, I;Kiyono, H
禁止的CD4(+)betabeta T细胞主要产生白细胞介素(IL)-4，是T细胞受体α链(TCRα)缺陷小鼠结肠炎发展的病理亚群。 H,4刺激初始CD4(+) T细胞通过激活信号转导子和转录激活子(STAT) 6诱导Th2发育。在本研究中，我们发现IL-4增强了从结肠炎TCRalpha(-/-)小鼠分离的CD4(+)betabeta T细胞中STAT6的表达，表明CD4(+)betabeta T细胞中的IL-4信号是由STAT6介导的。为了进一步研究STAT6在TCRα缺陷引起的结肠炎发展中的作用，我们通过将TCRα(-/-)小鼠和STAT6(-/-)小鼠杂交产生双缺陷小鼠。令人惊讶的是，STAT6 缺陷并没有导致 TCRa-/- 小鼠结肠炎严重程度降低。 STAT6缺陷的CD4(+)betabeta T细胞产生IL-4，在未患病的TCRα(-/-)和STAT6双缺陷小鼠中腹腔注射抗IL-4单克隆抗体可阻止结肠炎的形成，从而表明分化为Th2表型的细胞具有在STAT6缺失的情况下介导结肠炎发生的能力。
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.