title: Retinoic acid-producing, ex-vivo-generated human tolerogenic dendritic cells induce the proliferation of immunosuppressive B lymphocytes.
abstract: While much is known about tolerogenic dendritic cell effects on forkhead box protein 3 (FoxP3)⁺ regulatory T cells, virtually nothing is known about their effects on another arm of immunoregulation that is mediated by a subpopulation of immunosuppressive B cells. These cells suppress rheumatoid arthritis, lupus and inflammatory bowel disease in mice, and functional defects have been reported in human lupus. We show that co-stimulation-impaired tolerogenic dendritic cells that prevent and reverse type 1 diabetes mellitus induce the proliferation of human immunosuppressive B cells in vitro. We also show that the suppressive properties of these B cells concentrate inside the CD19⁺ CD24⁺ B cell population and more specifically inside the CD19⁺ CD24⁺ CD38⁺ regulatory B cell population. We discovered that B cell conversion into suppressive cells in vitro is partially dependent on dendritic cell production of retinoic acid and also that CD19⁺ CD24⁺ CD38⁺ B regulatory cells express retinoic acid receptors. Taken together, our data suggest a model whereby part of the immunosuppressive properties of human tolerogenic dendritic cells could be mediated by retinoic acid which, in addition to its known role in favouring T cell differentiation to FoxP3⁺ regulatory T cells, acts to convert B cells into immunosuppressive cells.
authors.affiliation: Department of Pediatrics, Division of Immunogenetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; RiMed Foundation, Palermo, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Di Caro
authors.forename: B
authors.initials: B
authors.lastname: Phillips
authors.forename: C
authors.initials: C
authors.lastname: Engman
authors.forename: J
authors.initials: J
authors.lastname: Harnaha
authors.forename: M
authors.initials: M
authors.lastname: Trucco
authors.forename: N
authors.initials: N
authors.lastname: Giannoukakis
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D018941:Antigens, CD19 / Q000378:metabolism; D060151:B-Lymphocytes, Regulatory / Q000276:immunology*; D051927:CD24 Antigen / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D007165:Immunosuppression Therapy; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014212:Tretinoin / Q000276:immunology / Q000378:metabolism
chemical_list: D018941:Antigens, CD19; D051927:CD24 Antigen; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D014212:Tretinoin; D051997:ADP-ribosyl Cyclase 1
keywords: B cells; antigen-presenting cells; autoimmunity; immunomodulation; immunosuppressive