Fig. 2. Multiple mechanisms are involved in Bregs functions.

a Through cell contact and anti-inflammatory cytokines, including IL-10, TGF-β, and IL-35, Bregs suppress CD4⁺ T-cell proliferation, induce Foxp3⁺ Tregs and Tr1 cells, and suppress Th1/17 differentiation and CD8⁺ effector T cells. b IL-10 and TGF-β secreted by Bregs hamper the antigen-presenting function and cytokine secretion of dendritic cells and M1 macrophages, and they possibly induce M2 macrophages. They also negatively regulate neutrophils and NK cells. c PD-L1 and FasL expressed on the surface of Bregs induce T-cell apoptosis through binding to PD-1 and Fas, respectively, together with cytokines IL-10 and IL-4