title: CD252 regulates mast cell mediated, CD1d-restricted NKT-cell activation in mice.
abstract: The interaction between tissue-resident mast cells (MCs) and recruited immune cells contributes to tissue immunosurveillance. However, the cells, mechanisms, and receptors involved in this crosstalk remain ill defined. Invariant natural killer T (iNKT) cells are CD1d-restricted innate lymphocytes that recognize glycolipid antigens and have emerged as critical players in immunity. Here, we show that primary mouse peritoneal MCs express surface CD1d, which is upregulated in vivo following administration of alpha-galactosylceramide. In contrast, in BM-derived MCs CD1d was found to be stored intracellularly and to relocate at the cell surface upon IgE-mediated degranulation. Activated BM-derived MCs expressing surface CD1d and loaded with alpha-galactosylceramide were found to induce iNKT-cell proliferation and the release of IFN-γ, IL-13, and IL-4 in a CD1d-restricted manner. Moreover, the costimulatory molecules CD48, CD137L, CD252, CD274, and CD275 affected MC-induced IFN-γ release and iNKT-cell proliferation. Interestingly, among the costimulatory molecules, CD48 and CD252 exhibited a distinctly regulatory activity on iNKT-cell release of both IFN-γ and IL-13. In conclusion, we demonstrate that the crosstalk between MCs and iNKT cells may regulate inflammatory immune responses.
authors.affiliation: Priority Area Asthma and Allergy, Airway Research Center North, German Center for Lung Research, Research Center Borstel, Borstel, Germany.
authors.forename: Nestor
authors.initials: N
authors.lastname: Gonzalez Roldan
authors.affiliation: Priority Area Asthma and Allergy, Airway Research Center North, German Center for Lung Research, Research Center Borstel, Borstel, Germany.
authors.forename: Zane
authors.initials: Z
authors.lastname: Orinska
authors.affiliation: Priority Area Asthma and Allergy, Airway Research Center North, German Center for Lung Research, Research Center Borstel, Borstel, Germany.
authors.forename: Hanno
authors.initials: H
authors.lastname: Ewers
authors.affiliation: Manchester Collaborative Centre for Inflammation Research (MCCIR), Institute of Inflammation and Repair, University of Manchester, Manchester, UK.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bulfone-Paus
mesh_terms: D000818:Animals; D055610:Antigens, CD1d / Q000235:genetics / Q000378:metabolism*; D002450:Cell Communication; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005699:Galactosylceramides / Q000008:administration & dosage; D005786:Gene Expression Regulation; D007113:Immunity, Innate / Q000187:drug effects; D056747:Immunomodulation; D008213:Lymphocyte Activation / Q000187:drug effects; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015166:Monitoring, Immunologic; D055611:Natural Killer T-Cells / Q000276:immunology*; D053278:OX40 Ligand / Q000235:genetics / Q000378:metabolism*
chemical_list: D055610:Antigens, CD1d; D016207:Cytokines; D005699:Galactosylceramides; D053278:OX40 Ligand; C089251:TNFSF4 protein, human; C493154:alpha-galactosylceramide
keywords: Glycolipid presentation ⋅ Immunoregulation ⋅ Mast cell ⋅ NKT cell