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

Boldison, Joanne, Camargo Da Rosa, Larissa, Davies, Joanne, Wen, Li and Wong, F. Susan ORCID: https://orcid.org/0000-0002-2812-8845 2020. Dendritic cells license regulatory B cells to produce IL-10 and mediate suppression of antigen-specific CD8 T cells. Cellular and Molecular Immunology 17 , 843 - 855. 10.1038/s41423-019-0324-z

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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:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	Nature Publishing Group
ISSN:	1672-7681
Date of First Compliant Deposit:	21 November 2019
Date of Acceptance:	23 October 2019
Last Modified:	08 Nov 2024 00:15
URI:	https://orca.cardiff.ac.uk/id/eprint/127020

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