title: Selective depletion of CD11c+CD11b+dendritic cells partially abrogates tolerogenic effects of intravenous MOG in murine EAE.
abstract: Intravenous (i.v.) injection of a soluble myelin antigen can induce tolerance, which effectively ameliorates experimental autoimmune encephalomyelitis (EAE). We have previously shown that i.v. myelin oligodendrocyte glycoprotein (MOG) induces tolerance in EAE and expands a subpopulation of tolerogenic CD11c+CD11b+dendritic cells (DCs) with an immature phenotype having low expression of IA and co-stimulatory molecules CD40, CD86, and CD80. Here, we further investigate the role of tolerogenic DCs in i.v. tolerance by injecting clodronate-loaded liposomes, which selectively deplete CD11c+CD11b+and immature DCs, but not CD11c+CD8+DCs and mature DCs. I.v. MOG-induced suppression of EAE was partially, yet significantly, blocked by CD11c+CD11b+DC depletion. While i.v. MOG inhibited IA, CD40, CD80, CD86 expression and induced TGF-β, IL-27, IL-10 production in CD11c+CD11b+DCs, these effects were abrogated after injection of clodronate-loaded liposomes. Depletion of CD11c+CD11b+DCs also precluded i.v. autoantigen-induced T-cell tolerance, such as decreased production of IL-2, IFN-γ, IL-17 and numbers of IL-2+, IFN-γ+, and IL-17+CD4+T cells, as well as an increased proportion of CD4+CD25+Foxp3+regulatory T cells and CD4+IL-10+Foxp3-Tr1 cells. CD11c+CD11b+DCs, through low expression of IA and costimulatory molecules as well as high expression of TGF-β, IL-27, and IL-10, play an important role in i.v. tolerance-induced EAE suppression.
authors.affiliation: Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA.|Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Limei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Zichen
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Bogoljub
authors.initials: B
authors.lastname: Ciric
authors.affiliation: Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Farinaz
authors.initials: F
authors.lastname: Safavi
authors.affiliation: Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Guang-Xian
authors.initials: GX
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA. A.M.Rostami@jefferson.edu.
authors.forename: Abdolmohamad
authors.initials: A
authors.lastname: Rostami
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D039521:CD11c Antigen / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D004002:Clodronic Acid / Q000008:administration & dosage; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007108:Immune Tolerance; D008081:Liposomes / Q000008:administration & dosage; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D039481:CD11b Antigen; D039521:CD11c Antigen; D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D008081:Liposomes; D063308:Myelin-Oligodendrocyte Glycoprotein; D004002:Clodronic Acid
keywords: Dendritic cell; Experimental autoimmune encephalomyelitis; Immune tolerance; Multiple sclerosis