Immunology Program, Benaroya Research Institute, Seattle, WA 98101, USA.
J Immunol. 2011 Dec 15;187(12):6176-9. doi: 10.4049/jimmunol.1102515. Epub 2011 Nov 14.
The neutralization of α4 integrin is currently used as treatment in several autoimmune diseases and is thought to prevent the entry of most immune cells in target tissues. In this study, we showed that selective deletion of α4 integrin in T cells did not prevent but delayed the development of experimental autoimmune encephalomyelitis. Whereas both Th1 and Th17 cells infiltrate the CNS of wild-type mice, T cells present in the CNS of mice lacking α4 integrin were mainly enriched in Th17 cells, suggesting that this T cell subset uses other integrins to access the CNS. In contrast, α4 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-α4 integrin Ab treatment may be more efficient in the treatment of Th1- rather than Th17-mediated disease.
α4 整合素的中和作用目前被用于治疗几种自身免疫性疾病，据认为可防止大多数免疫细胞进入靶组织。在这项研究中，我们表明，T 细胞中 α4 整合素的选择性缺失不仅没有阻止，反而延迟了实验性自身免疫性脑脊髓炎的发展。虽然 Th1 和 Th17 细胞都浸润野生型小鼠的中枢神经系统，但缺乏 α4 整合素的小鼠中枢神经系统中的 T 细胞主要富集 Th17 细胞，这表明该 T 细胞亚群使用其他整合素来进入中枢神经系统。相比之下，α4 整合素的表达对于 Th1 细胞进入中枢神经系统以及它们 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-α4 整合素 Ab 治疗可能在治疗 Th1 介导的疾病而非 Th17 介导的疾病方面更有效。
