title: Specialized proresolving mediators (SPMs) inhibit human B-cell IgE production.
abstract: Specialized proresolving mediators (SPMs) constitute a recently recognized class of bioactive molecules thatpromote the resolution of inflammation. We recently reported that the SPMs resolvin D1 (RvD1) and 17-hydroxydocosahexaenoic acid (17-HDHA) promote the differentiation of IgG-secreting B cells and enhance antibody-mediated immune responses. However, there is an important knowledge gap regarding whether or not SPMs regulate human B-cell IgE production, which is the key effector in diseases such as asthma and allergy. Therefore, we investigated whether a panel of diverse SPMs influences B-cell IgE production. An important finding was that 17-HDHA and RvD1 inhibit IgE production by human B cells and suppress the differentiation of naïve B cells into IgE-secreting cells by specifically blocking epsilon germline transcript. This effect is specific to human IgE, as the SPMs do not inhibit production of IgM and IgG and did not suppress other IL-4-upregulated genes. 17-HDHA and RvD1 act by stabilizing the transcriptional repressor B-cell lymphoma 6, which competes with STAT6 for binding at the epsilon germline transcript promoter. Overall, these new findings demonstrate that certain SPMs inhibit the differentiation of IgE-producing B cells, without being broadly immune suppressive, representing a novel class of potential therapeutics for IgE-driven diseases such as asthma and allergy.
authors.affiliation: Department of Microbiology and Immunology, University of Rochester, Rochester, NY, USA.
authors.forename: Nina
authors.initials: N
authors.lastname: Kim
authors.affiliation: Department of Microbiology and Immunology, University of Rochester, Rochester, NY, USA.
authors.forename: Sesquile
authors.initials: S
authors.lastname: Ramon
authors.affiliation: Division of Pulmonary and Critical Care Medicine, University of Rochester, Rochester, NY, USA.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Thatcher
authors.affiliation: Department of Environmental Medicine, University of Rochester, Rochester, NY, USA.
authors.forename: Collynn F
authors.initials: CF
authors.lastname: Woeller
authors.affiliation: Division of Pulmonary and Critical Care Medicine, University of Rochester, Rochester, NY, USA.|Department of Environmental Medicine, University of Rochester, Rochester, NY, USA.
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Sime
authors.affiliation: Department of Microbiology and Immunology, University of Rochester, Rochester, NY, USA.|Department of Environmental Medicine, University of Rochester, Rochester, NY, USA.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Phipps
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D015153:Blotting, Western; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D004281:Docosahexaenoic Acids / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000276:immunology; D007073:Immunoglobulin E / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C518399:resolvin D1; D004281:Docosahexaenoic Acids; D007073:Immunoglobulin E; C062894:17-hydroxy-4,7,10,13,15,19-docosahexaenoic acid
keywords: B cell; Human; IgE; Inflammation resolution; Proresolving mediator