title: Mesenchymal stem/stromal cells protect against autoimmunity via CCL2-dependent recruitment of myeloid-derived suppressor cells.
abstract: Exogenously administered mesenchymal stem/stromal cells (MSCs) suppress autoimmunity despite transient engraftment. However, the mechanism is unclear. In this study, we report a novel mechanism by which MSCs modulate the immune system by recruiting myeloid-derived suppressor cells in a mouse model of experimental autoimmune uveitis (EAU). Intravenous infusion of MSCs blocked EAU development and reduced Th1 and Th17 responses. Time course analysis revealed an increase of MHC class II(lo)Ly6G(-)Ly6C(hi)CD11b(+) cells in draining lymph nodes by MSCs. These Ly6C(hi)CD11b(+) cells suppressed CD4(+) cell proliferation and Th1/Th17 differentiation and induced CD4(+) cell apoptosis. Adoptive transfer of Ly6C(hi)CD11b(+) cells ameliorated EAU, whereas depletion of Ly6C(hi)CD11b(+) cells abrogated the effects of MSCs. 1.8% of MSCs were present in draining lymph nodes 1 d after infusion, and MSCs with CCL2 knockdown did not increase MHC class II(lo)Ly6G(-)Ly6C(hi)CD11b(+) cells and failed to attenuate EAU. Therefore, our findings demonstrate that MSCs suppress autoimmunity by recruiting myeloid-derived suppressor cells into sites of inflammation in a CCL2-dependent manner.
authors.affiliation: Department of Ophthalmology, Seoul National University Hospital, Seoul 110-744, Korea; Laboratory of Ocular Regenerative Medicine and Immunology, Biomedical Research Institute, Seoul National University Hospital, Seoul 110-744, Korea; and.
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Ophthalmology, Seoul National University Hospital, Seoul 110-744, Korea; Laboratory of Ocular Regenerative Medicine and Immunology, Biomedical Research Institute, Seoul National University Hospital, Seoul 110-744, Korea; and.
authors.forename: Jung Hwa
authors.initials: JH
authors.lastname: Ko
authors.affiliation: Department of Ophthalmology, Seoul National University Hospital, Seoul 110-744, Korea; Laboratory of Ocular Regenerative Medicine and Immunology, Biomedical Research Institute, Seoul National University Hospital, Seoul 110-744, Korea; and.
authors.forename: Hyun Jeong
authors.initials: HJ
authors.lastname: Jeong
authors.affiliation: Department of Ophthalmology, Seoul National University Hospital, Seoul 110-744, Korea; Laboratory of Ocular Regenerative Medicine and Immunology, Biomedical Research Institute, Seoul National University Hospital, Seoul 110-744, Korea; and.
authors.forename: Ah Young
authors.initials: AY
authors.lastname: Ko
authors.affiliation: Department of Ophthalmology, Seoul National University Hospital, Seoul 110-744, Korea; Laboratory of Ocular Regenerative Medicine and Immunology, Biomedical Research Institute, Seoul National University Hospital, Seoul 110-744, Korea; and.
authors.forename: Mee Kum
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Department of Ophthalmology, Seoul National University Hospital, Seoul 110-744, Korea; Laboratory of Ocular Regenerative Medicine and Immunology, Biomedical Research Institute, Seoul National University Hospital, Seoul 110-744, Korea; and.
authors.forename: Won Ryang
authors.initials: WR
authors.lastname: Wee
authors.affiliation: Transplantation Research Institute, Seoul National University College of Medicine, Seoul 110-744, Korea.
authors.forename: Sun-Ok
authors.initials: SO
authors.lastname: Yoon
authors.affiliation: Department of Ophthalmology, Seoul National University Hospital, Seoul 110-744, Korea; Laboratory of Ocular Regenerative Medicine and Immunology, Biomedical Research Institute, Seoul National University Hospital, Seoul 110-744, Korea; and jooyounoh77@gmail.com.
authors.forename: Joo Youn
authors.initials: JY
authors.lastname: Oh
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D015551:Autoimmunity / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000276:immunology*; D005260:Female; D055785:Gene Knockdown Techniques; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D051379:Mice; D022423:Myeloid Cells / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology
chemical_list: C111835:CCL2 protein, human; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D000949:Histocompatibility Antigens Class II