title: 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 (roquinsan/sanmice) 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 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/sanmice. 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/sanmice.
  
  
  
  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.
authors.affiliation: The Catholic University of Korea, Seoul, South Korea.
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Park
authors.affiliation: The Catholic University of Korea, Seoul, South Korea.
authors.forename: Sung-Hee
authors.initials: SH
authors.lastname: Lee
authors.affiliation: The Catholic University of Korea, Seoul, South Korea.
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Kim
authors.affiliation: The Catholic University of Korea, Seoul, South Korea.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Park
authors.affiliation: Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea. seungki73@catholic.ac.kr.
authors.forename: Seung-Ki
authors.initials: SK
authors.lastname: Kwok
authors.affiliation: The Catholic University of Korea, Seoul, South Korea. iammila@catholic.ac.kr.
authors.forename: Mi-La
authors.initials: ML
authors.lastname: Cho
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology; D015551:Autoimmunity / Q000187:drug effects / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D060151:B-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*; D018920:Coculture Techniques; D004247:DNA / Q000276:immunology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018858:Germinal Center; D016753:Interleukin-10 / Q000276:immunology; D007668:Kidney / Q000276:immunology / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008181:Lupus Nephritis / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D000072737:Myeloid-Derived Suppressor Cells / Q000276:immunology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D010950:Plasma Cells / Q000276:immunology; D011507:Proteinuria / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D044767:Ubiquitin-Protein Ligases / Q000235:genetics
chemical_list: D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D004791:Enzyme Inhibitors; C556062:IL10 protein, mouse; D016753:Interleukin-10; D004247:DNA; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C501406:Rc3h1 protein, mouse; D044767:Ubiquitin-Protein Ligases; D019331:NG-Nitroarginine Methyl Ester