Objectives: Although various studies have been performed on the function of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in RA, the results were conflicting. Here we were trying to clarify the role of PMN-MDSCs in the pathogenesis of RA and its specific mechanisms. Methods: We detected the frequencies and counts of PMN-MDSCs, TNF- + B cells, and Ki67 + B cells in spleens and inflamed joints of collagen-induced arthritis (CIA) mice using flow cytometry. The pathological role of PMN-MDSCs was examined by anti-Ly6G neutralizing antibodies against PMN-MDSCs or adoptive transfer of PMN-MDSCs. And the modulation of PMN-MDSCs on B cells was conducted by coculture assays, RNA-Seq, RT-qPCR, etc. The mechanism of BAFF regulating B cells was verified through Western Blot and flow cytometry. Results: PMN-MDSCs accumulated in the spleens and joints of CIA mice. PMN-MDSCs depletion could alleviate the arthritis severity, which was accompanied by decreased TNF- secretion and proliferation of B cells. And its adoptive transfer also facilitated disease progress. Furthermore, PMN-MDSCs from CIA mice had higher expression level of BAFF, which regulated TNF- expression, proliferation and apoptosis of B cells in vitro. What’s more, BAFF promoted phosphorylation of BTK/NF-B signaling pathway. And Ibrutinib (BTK inhibitor) could reverse the effect of BAFF on TNF- expression. Conclusions: Our study suggested that PMN-MDSCs enhanced disease severity of CIA and manipulated TNF- expression, proliferation and apoptosis of B cells via BAFF, furthermore, BAFF promoted TNF- expression through BTK/NF-B signaling pathway, which demonstrated a novel pathogenesis of PMN-MDSC in CIA.
According to reports, gut microbiota and metabolites regulate intestinal immune microenvironment. In recent years, an increasing number of studies reported that bile acids (BAs) of intestinal flora origin affects T helper cells and Treg cells. Th17 cells play a pro-inflammatory role and Treg cells usually act an immunosuppressive role. In this review, we emphatically summarized the influence and corresponding mechanism of different configurations of the LCA and DCA on intestinal Th17 cells, Treg cells and intestinal immune microenvironment. The regulation of BAs receptors G protein-coupled bile acid receptor 1 (GPBAR1/TGR5) and farnesoid X receptor (FXR) on immune cells and intestinal environment are elaborated. Furthermore, the potential clinical applications above were also concluded in three aspects. These above will help researchers better understand the effects of gut flora on the intestinal immune microenvironment via BAs and contribute to the development of new targeted drugs.