title: IL-10-Induced miR-155 Targets SOCS1 To Enhance IgE-Mediated Mast Cell Function.
abstract: IL-10 is an important regulatory cytokine that modulates a wide range of immune cells. Whereas it is best known for its ability to suppress immune responses, IL-10 has been found to be pathogenic in several human and animal studies of immune-mediated diseases. There is a considerable gap in our understanding of the molecular mechanisms behind the stimulatory effects of IL-10 during allergic inflammation. IL-10 treatment has been shown to suppress mast cell TNF production. In this study, we report that whereas TNF secretion was reduced, IL-10 surprisingly enhanced IgE-mediated protease and cytokine production both in vitro and in vivo. This stimulatory effect was consistent in mouse and human skin mast cells. IL-10 enhanced activation of the key FcεRI signaling proteins Stat5, JNK, and ERK. We demonstrate that IL-10 effects are dependent on Stat3 activation, eliciting miR-155 expression, with a resulting loss of suppressor of cytokine signaling-1. The importance of miR-155 was demonstrated by the inability of IL-10 to enhance anaphylaxis in miR-155-deficient mice. Taken together, our results reveal an IL-10-induced, Stat3-miR-155 signaling pathway that can promote mast cell responses.
authors.affiliation: Department of Biology, Virginia Commonwealth University, Richmond, VA 23284; and.
authors.forename: Amina Abdul
authors.initials: AA
authors.lastname: Qayum
authors.affiliation: Department of Biology, Virginia Commonwealth University, Richmond, VA 23284; and.
authors.forename: Anuya
authors.initials: A
authors.lastname: Paranjape
authors.affiliation: Department of Biology, Virginia Commonwealth University, Richmond, VA 23284; and.
authors.forename: Daniel
authors.identifier: 0000-0002-6837-3028
authors.initials: D
authors.lastname: Abebayehu
authors.affiliation: Department of Biology, Virginia Commonwealth University, Richmond, VA 23284; and.
authors.forename: Elizabeth Motunrayo
authors.initials: EM
authors.lastname: Kolawole
authors.affiliation: Department of Biology, Virginia Commonwealth University, Richmond, VA 23284; and.
authors.forename: Tamara T
authors.initials: TT
authors.lastname: Haque
authors.affiliation: Department of Biology, Virginia Commonwealth University, Richmond, VA 23284; and.
authors.forename: Jamie Josephine Avila
authors.initials: JJ
authors.lastname: McLeod
authors.affiliation: Department of Biology, Virginia Commonwealth University, Richmond, VA 23284; and.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Spence
authors.affiliation: Department of Biology, Virginia Commonwealth University, Richmond, VA 23284; and.
authors.forename: Heather L
authors.initials: HL
authors.lastname: Caslin
authors.affiliation: Department of Biology, Virginia Commonwealth University, Richmond, VA 23284; and.
authors.forename: Marcela T
authors.initials: MT
authors.lastname: Taruselli
authors.affiliation: Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, SC 29208.
authors.forename: Alena P
authors.initials: AP
authors.lastname: Chumanevich
authors.affiliation: Department of Biology, Virginia Commonwealth University, Richmond, VA 23284; and.
authors.forename: Bianca
authors.initials: B
authors.lastname: Baker
authors.affiliation: Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, SC 29208.
authors.forename: Carole A
authors.identifier: 0000-0003-1380-9186
authors.initials: CA
authors.lastname: Oskeritzian
authors.affiliation: Department of Biology, Virginia Commonwealth University, Richmond, VA 23284; and jjryan@vcu.edu.
authors.forename: John J
authors.initials: JJ
authors.lastname: Ryan
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D007073:Immunoglobulin E / Q000276:immunology*; D016753:Interleukin-10 / Q000276:immunology*; D008407:Mast Cells / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics* / Q000276:immunology; D000071222:Suppressor of Cytokine Signaling 1 Protein / Q000235:genetics*
chemical_list: D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D016753:Interleukin-10; D007073:Immunoglobulin E