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CD226 ligation protects against EAE by promoting IL-10 expression via regulation of CD4+ T cell differentiation.


ABSTRACT: 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.

SUBMITTER: Zhang R 

PROVIDER: S-EPMC4991380 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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CD226 ligation protects against EAE by promoting IL-10 expression via regulation of CD4+ T cell differentiation.

Zhang Rong R   Zeng Hanyu H   Zhang Yun Y   Chen Kun K   Zhang Chunmei C   Song Chaojun C   Fang Liang L   Xu Zhuwei Z   Yang Kun K   Jin Boquan B   Wang Qintao Q   Chen Lihua L  

Oncotarget 20160401 15


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 p  ...[more]

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