CD226 ligation protects against EAE by promoting IL-10 expression via regulation of CD4+ T cell differentiation.
CD226 ligation protects against EAE by promoting IL-10 expression via regulation of CD4+ T cell differentiation.
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CD226 连接通过调节 CD4 T 细胞分化促进 IL-10 表达来预防 EAE
DOI：
10.18632/oncotarget.7834
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发表时间：
2016-04-12
期刊：
影响因子：
--
通讯作者：
Chen L
中科院分区：
文献类型：
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作者：
Zhang R;Zeng H;Zhang Y;Chen K;Zhang C;Song C;Fang L;Xu Z;Yang K;Jin B;Wang Q;Chen L
针对CD 226的治疗可以改善实验性自身免疫性脑脊髓炎（EAE），这是广泛接受的MS模型。我们发现，用抗CD 226阻断mAb LeoA 1阻断CD 226，可有效促进人外周血单核细胞（PBMC）或混合淋巴细胞培养（MLC）系统中IL-10的产生，显著诱导CD 4 +IL-10+ T细胞分化，同时抑制Th 1和Th 17的产生。此外，体内给予CD 226 pAb通过促进IL-10产生和调节T细胞分化减少小鼠中EAE的发作。同时，CD 226基因敲除小鼠EAE的发病率和严重程度均低于对照组，血清IL-10表达水平高于对照组。这些新的发现证实了CD 226在介导自身免疫性疾病如EAE中起着关键作用。此外，据我们所知，我们首次表明IL-10是CD 226连接对EAE的抑制作用的重要贡献者。
Treatment targeting CD226 can ameliorate experimental autoimmune encephalomyelitis (EAE), the widely accepted model of MS. However, the mechanisms still need to be elucidated. Here we showed that CD226 blockage by anti-CD226 blocking mAb LeoA1 efficiently promoted IL-10 production in human peripheral blood monocytes (PBMC) or in mixed lymphocyte culture (MLC) system, significantly induced the CD4+IL-10+ T cell differentiation while suppressing the generation of Th1 and Th17. Furthermore, CD226 pAb administration in vivo reduced the onset of EAE in mice by promoting IL-10 production and regulating T cell differentiation. Concomitantly, the onset and severity of EAE were reduced and the serum IL-10 expression levels were increased in CD226 knockout mice than that in control mice when both received EAE induction. These novel findings confirmed that CD226 played a pivotal role in mediating autoimmune diseases such as EAE. Furthermore, to our knowledge, we show for the first time that IL-10 is an important contributor in the inhibitory effects of CD226 ligation on EAE.