title: Distinct cytokines balance the development of regulatory T cells and interleukin-10-producing regulatory B cells.
abstract: Regulatory T cells have been well described and the factors regulating their development and function have been identified. Recently, a growing body of evidence has documented the existence of interleukin-10 (IL-10) -producing B cells, which are called regulatory B10 cells. These cells attenuate autoimmune, inflammatory and transplantation reactions, and the main mechanism of their inhibitory action is the production of IL-10. We show that the production of IL-10 by lipopolysaccharide-stimulated B cells is significantly enhanced by IL-12 and interferon-γ and negatively regulated by IL-21 and transforming growth factor-β. In addition, exogenous IL-10 also inhibits B-cell proliferation and the expression of the IL-10 gene in lipopolysaccharide-stimulated B cells. The negative autoregulation of IL-10 production is supported by the observation that the inclusion of anti-IL-10 receptor monoclonal antibody enhances IL-10 production and the proliferation of activated B cells. The effects of cytokines on IL-10 production by B10 cells did not correlate with their effects on B-cell proliferation or on IL-10 production by T cells or macrophages. The cytokine-induced changes in IL-10 production occurred on the level of IL-10 gene expression, as confirmed by increased or decreased IL-10 mRNA expression in the presence of a particular cytokine. The regulatory cytokines modulate the number of IL-10-producing cells rather than augmenting or decreasing the secretion of IL-10 on a single-cell level. Altogether these data show that the production of IL-10 by B cells is under the strict regulatory control of cytokines and that individual cytokines differentially regulate the development and activity of regulatory T cells and IL-10-producing regulatory B cells.
authors.affiliation: Department of Transplantation Immunology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic; Faculty of Science, Charles University, Prague, Czech Republic.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Holan
authors.forename: Alena
authors.initials: A
authors.lastname: Zajicova
authors.forename: Eliska
authors.initials: E
authors.lastname: Javorkova
authors.forename: Peter
authors.initials: P
authors.lastname: Trosan
authors.forename: Milada
authors.initials: M
authors.lastname: Chudickova
authors.forename: Michaela
authors.initials: M
authors.lastname: Pavlikova
authors.forename: Magdalena
authors.initials: M
authors.lastname: Krulova
mesh_terms: D000818:Animals; D060151:B-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; C573415:IFNG protein, human; C556062:IL10 protein, mouse; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011994:Recombinant Proteins; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma
keywords: B cells; autoregulation; cytokines; immunosuppression; interleukin-10 production