title: Activated mast cells synthesize and release soluble ST2-a decoy receptor for IL-33.
abstract: IL-33 released from damaged cells plays a central role in allergic inflammation by acting through its membrane-bound receptor, ST2 receptor (ST2L). IL-33 activity can be neutralized by the soluble spliced variant of ST2 (sST2) that has been associated with allergic inflammation but its source is not well defined. We investigated whether mast cells (MCs) are a significant source of sST2 following activation through FcεRI or ST2. We find that antigen and IL-33 induce substantial production and release of sST2 from human and mouse MCs in culture and do so synergistically when added together or in combination with stem cell factor. Moreover, increases in circulating sST2 during anaphylaxis in mice were dependent on the presence of MCs. Human MCs activated via FcεRI failed to generate IL-33 and IL-33 produced by mouse bone marrow-derived MCs was retained within the cells. Therefore, FcεRI-mediated sST2 production is independent of MC-derived IL-33 acting in an autocrine manner. These results are consistent with the conclusion that both mouse and human MCs when activated are a significant inducible source of sST2 but not IL-33 and thus have the ability to modulate the biologic impact of IL-33 produced locally by other cell types during allergic inflammation.
authors.affiliation: Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Geethani
authors.initials: G
authors.lastname: Bandara
authors.affiliation: Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Beaven
authors.affiliation: Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Ana
authors.initials: A
authors.lastname: Olivera
authors.affiliation: Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Alasdair M
authors.initials: AM
authors.lastname: Gilfillan
authors.affiliation: Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Dean D
authors.initials: DD
authors.lastname: Metcalfe
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D007249:Inflammation / Q000276:immunology; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33 / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D060888:Real-Time Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000276:immunology* / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology
chemical_list: C079241:IL1RL1 protein, human; C486189:Il1rl1 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D011956:Receptors, Cell Surface; D018123:Receptors, Interleukin
keywords: Antigen; Human mast cells; IL-33; Stem cell factor; sST2