Myeloid-Derived Suppressor Cells Induce the Expansion of Regulatory B Cells and Ameliorate Autoimmunity in the Sanroque Mouse Model of Systemic Lupus Erythematosus.

Abstract

This study was undertaken to assess the effect of myeloid-derived suppressor cells (MDSCs) on various B cell subsets, including regulatory B cells, as well as to assess the potential therapeutic effects of MDSC infusion in an animal model of systemic lupus erythematosus (SLE). Splenocytes were cultured with MDSCs, and the populations of various B cells and effector T cell subsets were analyzed by flow cytometry. Lupus mice (roquin^san/san mice) were treated intravenously with MDSCs obtained from C57BL/6 mice, and the levels of serum autoantibodies, degree of proteinuria, histologic changes in the kidney, and populations of various B cell and T cell subsets in the spleen were analyzed. Coculture of MDSCs with splenocytes from C57BL/6 mice resulted in an expansion of the population of interleukin-10-producing B cells. The expansion of regulatory B cells was completely blocked by the addition of N^G -monomethyl-l-arginine, an inhibitor of inducible nitric oxide synthase (iNOS). Infusion of MDSCs resulted in a reduction of serum anti-double-stranded DNA antibody levels and degree of proteinuria and an improvement in renal pathology in the roquin^san/san mice. MDSC coculture also resulted in a decrease in the population of effector B cells, such as germinal center B cells and plasma cells. Moreover, infusion of MDSCs resulted in an expansion of the regulatory B cell population as well as a decrease in follicular helper T cells, Th1 cells, and Th17 cells in the spleens of roquin^san/san mice. Our results indicate the MDSCs induce expansion of regulatory B cells via iNOS and ameliorate autoimmunity in a murine model of SLE. These findings indicate that MDSCs may be a promising therapeutic strategy for targeting B cell-mediated autoimmune diseases.