title: Intravenous transfer of apoptotic cell-treated dendritic cells leads to immune tolerance by blocking Th17 cell activity.
abstract: Apoptotic cell-induced tolerogenic dendritic cells (DCs) play an important role in induction of peripheral tolerance in vivo; however, the mechanisms of immune tolerance induced by these DCs are poorly understood. Here we show that treatment of apoptotic cells modulates expression of inflammation- and tolerance-associated molecules including Gr-1, B220, CD205 and galectin-1 on bone marrow-derived DCs. In addition, apoptotic cell-treated DCs suppress secretion of cytokines produced by Th17 cells. Our data also demonstrate that i.v. transfer of apoptotic cell-treated DCs blocks EAE development and down-regulates production of inflammatory cytokines such as IL-17A and IL-17F in CD4+ T cells. These results suggest that apoptotic cell-treated DCs may inhibit activity of Th17 cells via down-regulation of inflammatory cytokine production, thereby affecting EAE development in vivo. Our results reveal a potential mechanism of immune tolerance mediated by apoptotic cell-treated DCs and the possible use of apoptotic cell-treated DCs to treat autoimmune diseases such as MS/EAE.
authors.affiliation: Department of Neurology, Thomas Jefferson University, 900 Walnut Street, Philadelphia, PA 19107, USA. fang.zhou@uqconnect.edu.au
authors.forename: Fang
authors.initials: F
authors.lastname: Zhou
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Lauretti
authors.forename: Antonio
authors.initials: A
authors.lastname: di Meco
authors.forename: Bogoljub
authors.initials: B
authors.lastname: Ciric
authors.forename: Patricia
authors.initials: P
authors.lastname: Gonnella
authors.forename: Guang-Xian
authors.initials: GX
authors.lastname: Zhang
authors.forename: Abdolmohamad
authors.initials: A
authors.lastname: Rostami
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D017209:Apoptosis / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000628:therapy*; D005260:Female; D037483:Galectin 1 / Q000096:biosynthesis; D007108:Immune Tolerance / Q000276:immunology*; D007167:Immunotherapy; D037181:Lectins, C-Type / Q000096:biosynthesis; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D015778:Minor Histocompatibility Antigens; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000008:administration & dosage / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D019707:Receptors, Chemokine / Q000096:biosynthesis; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D016207:Cytokines; C093569:DEC-205 receptor; D037483:Galectin 1; C503133:Gr-1 protein, mouse; D037181:Lectins, C-Type; D015778:Minor Histocompatibility Antigens; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D019707:Receptors, Chemokine; C445081:myelin oligodendrocyte glycoprotein (35-55); D017493:Leukocyte Common Antigens