Dendritic cells license regulatory B cells to produce IL-10 and mediate suppression of antigen-specific CD8 T cells
| Autor: | Joanne Davies, Larissa Camargo da Rosa, F. Susan Wong, Li Wen, Joanne Boldison |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Lipopolysaccharides
0301 basic medicine Regulatory B cells Immunology Nod CD8-Positive T-Lymphocytes Biology Article Epitopes 03 medical and health sciences 0302 clinical medicine Antigens CD Mice Inbred NOD Immune Tolerance Animals Insulin Immunology and Allergy Cytotoxic T cell NOD mice Immunosuppression Therapy B-Lymphocytes Regulatory Innate immune system Models Immunological Cell Differentiation Dendritic Cells Dendritic cell Interleukin-10 Cell biology Interleukin 10 Diabetes Mellitus Type 1 Phenotype 030104 developmental biology Infectious Diseases TLR4 Cytokines 030215 immunology |
| Zdroj: | Cell Mol Immunol |
| ISSN: | 2042-0226 1672-7681 |
| DOI: | 10.1038/s41423-019-0324-z |
| Popis: | Regulatory B cells (Bregs) suppress and reduce autoimmune pathology. However, given the variety of Breg subsets, the role of Bregs in the pathogenesis of type 1 diabetes is still unclear. Here, we dissect this fundamental mechanism. We show that natural protection from type 1 diabetes in nonobese diabetic (NOD) mice is associated with increased numbers of IL-10-producing B cells, while development of type 1 diabetes in NOD mice occurs in animals with compromised IL-10 production by B cells. However, B cells from diabetic mice regain IL-10 function if activated by the innate immune receptor TLR4 and can suppress insulin-specific CD8 T cells in a dendritic cell (DC)-dependent, IL-10-mediated fashion. Suppression of CD8 T cells is reliant on B-cell contact with DCs. This cell contact results in deactivation of DCs, inducing a tolerogenic state, which in turn can regulate pathogenic CD8 T cells. Our findings emphasize the importance of DC–Breg interactions during the development of type 1 diabetes. |
| Databáze: | OpenAIRE |
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