Cutting edge: loss of α4 integrin expression differentially affects the homing of Th1 and Th17 cells.

Cutting edge: loss of α4 integrin expression differentially affects the homing of Th1 and Th17 cells.
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DOI:
10.4049/jimmunol.1102515
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发表时间:
2011-12-15
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Bettelli E
Bettelli E
中科院分区:
其他
文献类型:
--
作者:
Glatigny S;Duhen R;Oukka M;Bettelli E

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α 4整联蛋白的中和目前被用作几种自身免疫性疾病的治疗,并且被认为可以阻止大多数免疫细胞进入靶组织。在这里,我们表明,选择性删除α 4整合素在T细胞不能防止,但延迟实验性自身免疫性脑脊髓炎(EAE)的发展。尽管Th1和Th17细胞都浸润野生型小鼠的中枢神经系统(CNS),但缺乏α 4整联蛋白的小鼠的CNS中存在的T细胞主要富集在Th17细胞中,这表明该T细胞亚群使用其他整联蛋白进入CNS。相反,α 4整联蛋白的表达对于Th1细胞进入CNS和其Th1相关遗传程序的稳定性是重要的。因此,我们的数据表明,抗α 4整联蛋白抗体治疗可能更有效地治疗Th1而不是Th17介导的疾病。
The neutralization of alpha 4 integrin is currently used as treatment in several autoimmune diseases and is thought to prevent the entry of most immune cells in target tissues. Here, we showed that selective deletion of alpha4 integrin in T cells did not prevent but delayed the development of experimental autoimmune encephalomyelitis (EAE). Whereas both Th1 and Th17 cells infiltrate the central nervous system (CNS) of wild type mice, T cells present in the CNS of mice lacking alpha4 integrin were mainly enriched in Th17 cells suggesting that this T cell subset uses other integrins to access the CNS. In contrary, alpha4 integrin expression is important for Th1 cells to enter the CNS and for the stability of their Th1 associated genetic program. Therefore, our data suggest that anti-alpha4 integrin antibody treatment may be more efficient in the treatment of Th1 rather than Th17 mediated disease.
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