title: 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.
authors.affiliation: Department of Immunology, The Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.|State Key Laboratory of Military Stomatology, Department of Periodontology, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Immunology, The Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors.forename: Hanyu
authors.initials: H
authors.lastname: Zeng
authors.affiliation: Department of Immunology, The Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurobiology, The Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors.forename: Kun
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Immunology, The Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Immunology, The Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors.forename: Chaojun
authors.initials: C
authors.lastname: Song
authors.affiliation: Department of Immunology, The Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Fang
authors.affiliation: Department of Immunology, The Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors.forename: Zhuwei
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Immunology, The Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors.forename: Kun
authors.initials: K
authors.lastname: Yang
authors.affiliation: Department of Immunology, The Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors.forename: Boquan
authors.initials: B
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Periodontology, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors.forename: Qintao
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Immunology, The Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood / Q000276:immunology / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D000098862:T Lineage-Specific Activation Antigen 1
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D000098862:T Lineage-Specific Activation Antigen 1; D016207:Cytokines; D016753:Interleukin-10
keywords: CD226; CD4+ T cells; EAE; IL-10; Immune response; Immunity; Immunology and Microbiology Section; iTreg