Dendritic cells license regulatory B cells to produce IL-10 and mediate suppression of antigen-specific CD8 T cells

Boldison, J., Camargo da Rosa, L. , Davies, J., Wen, L. and Wong, F. S. (2019) Dendritic cells license regulatory B cells to produce IL-10 and mediate suppression of antigen-specific CD8 T cells. Cellular and Molecular Immunology, 17(8), pp. 843-855. (doi: 10.1038/s41423-019-0324-z) (PMID:31728048) (PMCID:PMC7395736)

Abstract

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.

• Item Type: Articles
• Additional Information: This work was funded by the Medical Research Council (UK) (MR/K021141/1 to FSW). LCDR was funded by a studentship from Cnpq (Conselho Nacional de Pesquisa, Brazil, grant #245609/2012-1).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Camargo da Rosa, Dr Larissa
• Authors: Boldison, J., Camargo da Rosa, L., Davies, J., Wen, L., and Wong, F. S.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Cellular and Molecular Immunology
• Publisher: Nature Publishing Group
• ISSN: 1672-7681
• ISSN (Online): 2042-0226
• Copyright Holders: Copyright © CSI and USTC 2019
• First Published: First published in Cellular and Molecular Immunology 17(8):843-855
• Publisher Policy: Reproduced under a Creative Commons licence