Therapeutic targeting of gut-originating regulatory B cells in neuroinflammatory diseases.

Regulatory B cells (Bregs) are immunosuppressive cells that support immunological tolerance by the production of interleukin (IL)-10, IL-35, and transforming growth factor β (TGF-β). Bregs arise from different developmental stages in response to inflammatory stimuli. In that regard, mounting evidence points towards a direct influence of gut microbiota on mucosal B cell development, activation, and regulation in health and disease. While an increasing number of diseases are associated with alterations in gut microbiome (dysbiosis), little is known about the role of microbiota on Breg development and induction in neuroinflammatory disorders. Notably, gut-originating, IL-10- and immunoglobulin A (IgA)-producing regulatory plasma cells have recently been demonstrated to egress from the gut to suppress inflammation in the central nervous system (CNS) raising fundamental questions about the triggers and functions of mucosal-originating Bregs in systemic inflammation. Advancing our understanding of regulatory B cells in neuroinflammatory diseases could lead to novel therapeutic approaches. Here, we summarize main aspects about regulatory B cell differentiation and functions and evidence about their involvement in neuroinflammatory diseases. Further, we highlight current data of gut-originating regulatory B cells and their microbial interactions and discuss future microbiota-/regulatory B cell-targeted therapies in immune-mediated diseases. This article is protected by copyright. All rights reserved.