Min-Jung Park1, Sung-Hee Lee1, Eun-Kyung Kim1, Eun-Jung Lee1, Sung-Hwan Park2, Seung-Ki Kwok3, Mi-La Cho4. 1. The Catholic University of Korea, Seoul, South Korea. 2. Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea. 3. Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea. seungki73@catholic.ac.kr. 4. The Catholic University of Korea, Seoul, South Korea. iammila@catholic.ac.kr.
Abstract
OBJECTIVE: 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). METHODS: Splenocytes were cultured with MDSCs, and the populations of various B cells and effector T cell subsets were analyzed by flow cytometry. Lupus mice (roquinsan/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. RESULTS: 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 NG -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 roquinsan/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 roquinsan/san mice. CONCLUSION: 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.
OBJECTIVE: 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). METHODS: Splenocytes were cultured with MDSCs, and the populations of various B cells and effector T cell subsets were analyzed by flow cytometry. Lupus mice (roquinsan/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. RESULTS: 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 NG -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 roquinsan/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 roquinsan/san mice. CONCLUSION: 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.