CD43 regulates Th2 differentiation and inflammation
CD43 regulates Th2 differentiation and inflammation
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DOI：
10.4049/jimmunol.180.11.7385
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发表时间：
2008-06-01
影响因子：
4.4
通讯作者：
Sperling, Anne I.
中科院分区：
文献类型：
--
作者：
Cannon, Judy L.;Collins, Amelie;Sperling, Anne I.
CD 43是一种高度糖基化的跨膜蛋白，调节T细胞活化。CD 43（-/-）T细胞是过度增殖的，并且已经发现CD 43的胞质尾区足以重建野生型增殖水平，这表明了细胞内机制。在这项研究中，我们报告说，在TCR连接CD 43（-/-）T细胞表现出酪氨酸磷酸化没有增加，但减少钙流量。有趣的是，CD 43（-/-）T细胞在体外优先分化为Th 2细胞，并且CD 43（-/-）T细胞显示增加的加塔-3易位到细胞核中。在体内，CD 43（-/-）小鼠在两种不同的Th 2介导的过敏性气道疾病模型中表现出炎症增加。相比之下，在Th 1介导的糖尿病中，非肥胖糖尿病CD 43（-/-）小鼠在疾病发作或进展方面与野生型小鼠没有显著差异。Th 1诱导的MOG（35-55）实验性自身免疫性脑脊髓炎在CD 43（-/-）小鼠中也正常。尽管如此，当在体外用MOG（35-55）再刺激时，CD 43（-/-）小鼠产生更多的IL-5，并表现出降低的迟发型超敏反应。总之，这些数据表明，虽然CD 43（-/-）T细胞优先分化为Th 2细胞，这种反应是不足以保护免受Th 1介导的自身免疫反应。
CD43 is a highly glycosylated transmembrane protein that regulates T cell activation. CD43(-/-) T cells are hyperproliferative and the cytoplasmic tail of CD43 has been found to be sufficient to reconstitute wild-type proliferation levels, suggesting an intracellular mechanism. In this study, we report that upon TCR ligation CD43(-/-) T cells demonstrated no increase in tyrosine phosphorylation but a decreased calcium flux. Interestingly, CD43(-/-) T cells preferentially differentiated into Th2 cells in vitro, and CD43(-/-) T cells show increased GATA-3 translocation into the nucleus. In vivo, CD43(-/-) mice exhibited increased inflammation in two separate models of Th2-mediated allergic airway disease. In contrast, in Th1-mediated diabetes, nonobese diabetic CD43(-/-) mice did not significantly differ from wild-type mice in disease onset or progression. Th1-induced experimental autoimmune encephalomyelitis to MOG(35-55) was also normal in the CD43(-/-) mice. Nonetheless, the CD43(-/-) mice produced more IL-5 when restimulated with MOG(35-55) in vitro and demonstrated decreased delayed-type hypersensitivity responses. Together, these data demonstrate that although CD43(-/-) T cells preferentially differentiate into Th2 cells, this response is not sufficient to protect against Th1-mediated autoimmune responses.