title: IL-10-conditioned dendritic cells prevent autoimmune diabetes in NOD and humanized HLA-DQ8/RIP-B7.1 mice.
abstract: This study was to determine whether BMDCs cultured in the presence of IL-10 (G/10-DCs) could promote T cell tolerance and prevent autoimmune diabetes in two different animal models of T1D. Our results showed that G/10-DCs suppressed both insulitis and spontaneous diabetes in NOD and HLA-DQ8/RIP-B7.1 mice. The suppression was likely to be mediated by T cells, as we found that regulatory CD4(+)CD25(+)Foxp3(+) cells were significantly increased in G/10-DC treated animals. In vivo, the G/10-DCs inhibited diabetogenic T cell proliferation; in vitro, they had reduced expression of costimulatory molecules and produced little IL-12/23 p40 or IL-6 but a large amount of IL-10 when compared with DCs matured in the presence of IL-4 (G/4-DC). We conclude that IL-10-treated DCs are tolerogenic and induce islet-directed immune tolerance, which was likely to be mediated by T regulatory cells. This non-antigen-specific DC-based approach offers potential for a new therapeutic intervention in T1D.
authors: Yale University School of Medicine, Department of Internal Medicine, Section of Endocrinology, USA.
authors: Ningwen
authors: N
authors: Tai
authors: Hisafumi
authors: H
authors: Yasuda
authors: Yufei
authors: Y
authors: Xiang
authors: Li
authors: L
authors: Zhang
authors: Daniel
authors: D
authors: Rodriguez-Pinto
authors: Koichi
authors: K
authors: Yokono
authors: Robert
authors: R
authors: Sherwin
authors: F Susan
authors: FS
authors: Wong
authors: Masao
authors: M
authors: Nagata
authors: Li
authors: L
authors: Wen
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D018122:B7-1 Antigen / Q000276:immunology*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000517:prevention & control*; D004195:Disease Models, Animal; D005260:Female; D006683:HLA-DQ Antigens / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D016130:Immunophenotyping; D050417:Insulin-Secreting Cells / Q000276:immunology*; D016753:Interleukin-10 / Q000276:immunology / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D013047:Specific Pathogen-Free Organisms; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D018122:B7-1 Antigen; D006683:HLA-DQ Antigens; C109756:HLA-DQ8 antigen; C556062:IL10 protein, mouse; D016753:Interleukin-10