Introduction
Rheumatoid arthritis (RA) is one of the most prevalent chronic autoimmune diseases, which involves the joints and even cause cartilage and bone damage(1). Autoimmunity and inflammation play important role in the pathogenesis of RA, however the precise mechanism is still unclear(1).
Myeloid-derived suppressor cells (MDSC) are heterogeneous myeloid cell populations that expand in tumors(2), infections (3), autoimmune diseases(4), and other abnormal conditions. The term ‘myeloid-derived suppressor cells’ was first coined in 2007, indicating its characteristics of myeloid origin and immunosuppressive function(5). MDSCs in mice express both CD11b and Gr-1 markers and have two subgroups: polymorphonuclear MDSCs (PMN-MDSCs) (CD11b+Ly6G+Ly6Clow) and mononuclear MDSCs (M-MDSCs) (CD11b+Ly6G-Ly6Chigh)(6). The role of MDSC in RA pathogenesis is controversial due to their heterogeneity, and some researchers hold the view that MDSCs are protective in RA(7, 8) by inhibiting the proliferation of T cells and B cells, while others believe they are proinflammatory(9, 10). PMN-MDSCs account for the majority of MDSCs in collagen-induced arthritis (CIA), and studies have found that PMN-MDSCs have a therapeutic impact in CIA mice(8, 11). However, we found that PMN-MDSCs play a distinct role in CIA. Therefore, we aimed to explore the mechanism underlying PMN-MDSC-mediated CIA.
The pivotal role of B cells in RA is clearly established by the presence of disease-specific autoantibodies and efficacy of B cell-targeting biological agents(12). A recent study showed that activated B cells also produce cytokines as well as antibodies(12), and B cell-derived TNF could control the development of autoantibodies and regulate the severity of CIA, whereas T cell-derived TNF is dispensable during arthritis(13). Qin et al(14) also found that age-associated B cells induced the activation of fibroblast-like synoviocytes (FLS) via TNF-𝛂, which indicated the important role of TNF-𝛂+ B cells in the pathogenesis of RA. Previous studies mainly focused on the PMN-MDSC regulating T cells, less researches have been done on regulating B cells, so we want to add something to this aspect.
Here, we first found that PMN-MDSCs were proinflammatory in CIA model, which could facilitate TNF-𝛂 secretion and proliferation of B cells, and inhibit apoptosis of B cells. Thus, our findings explained the pathogenic role of PMN-MDSCs and its regulation of B cells in RA, which provided a novel mechanism of RA.