Oncotarget

Research Papers: Immunology:

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

Rong Zhang, Hanyu Zeng, Yun Zhang, Kun Chen, Chunmei Zhang, Chaojun Song, Liang Fang, Zhuwei Xu, Kun Yang, Boquan Jin, Qintao Wang and Lihua Chen _

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Oncotarget. 2016; 7:19251-19264. https://doi.org/10.18632/oncotarget.7834

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Abstract

Rong Zhang1,2,*, Hanyu Zeng1,*, Yun Zhang1,*, Kun Chen3, Chunmei Zhang1, Chaojun Song1, Liang Fang1, Zhuwei Xu1, Kun Yang1, Boquan Jin1, Qintao Wang2 and Lihua Chen1

1 Department of Immunology, The Fourth Military Medical University, Xi’an, Shaanxi, P.R. China

2 State Key Laboratory of Military Stomatology, Department of Periodontology, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, P.R. China

3 Department of Neurobiology, The Fourth Military Medical University, Xi’an, Shaanxi, P.R. China

* These authors have contributed equally to this work

Correspondence to:

Lihua Chen, email:

Qintao Wang, email:

Keywords: CD226, CD4+ T cells, IL-10, EAE, iTreg, Immunology and Microbiology Section, Immune response, Immunity

Received: August 19, 2015 Accepted: January 29, 2016 Published: March 01, 2016

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.


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