title: Invariant NKT Cell Activation Is Potentiated by Homotypictrans-Ly108 Interactions.
abstract: Invariant NKT (iNKT) cells are innate lymphocytes that respond to glycolipids presented by the MHC class Ib molecule CD1d and are rapidly activated to produce large quantities of cytokines and chemokines. iNKT cell development uniquely depends on interactions between double-positive thymocytes that provide key homotypic interactions between signaling lymphocyte activation molecule (SLAM) family members. However, the role of SLAM receptors in the differentiation of iNKT cell effector subsets and activation has not been explored. In this article, we show that C57BL/6 mice containing the New Zealand BlackSlamlocus have profound alterations in Ly108, CD150, and Ly9 expression that is associated with iNKT cell hyporesponsiveness. This loss of function was only apparent when dendritic cells and iNKT cells had a loss of SLAM receptor expression. Using small interfering RNA knockdowns and peptide-blocking strategies, we demonstrated thattrans-Ly108 interactions between dendritic cells and iNKT cells are critical for robust activation. LY108 costimulation similarly increased human iNKT cell activation. Thus, in addition to its established role in iNKT cell ontogeny, Ly108 regulates iNKT cell function in mice and humans.
authors.affiliation: Krembil Research Institute, University Health Network, Toronto, Ontario M5T 2S8, Canada.|Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada; and.
authors.forename: Yuriy
authors.initials: Y
authors.lastname: Baglaenko
authors.affiliation: Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada; and.
authors.forename: Mayra
authors.initials: M
authors.lastname: Cruz Tleugabulova
authors.affiliation: Krembil Research Institute, University Health Network, Toronto, Ontario M5T 2S8, Canada.|Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada; and.
authors.forename: Eric
authors.initials: E
authors.lastname: Gracey
authors.affiliation: Krembil Research Institute, University Health Network, Toronto, Ontario M5T 2S8, Canada.|Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada; and.
authors.forename: Nafiseh
authors.initials: N
authors.lastname: Talaei
authors.affiliation: Krembil Research Institute, University Health Network, Toronto, Ontario M5T 2S8, Canada.|Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada; and.
authors.forename: Kieran Patricia
authors.initials: KP
authors.lastname: Manion
authors.affiliation: Krembil Research Institute, University Health Network, Toronto, Ontario M5T 2S8, Canada.
authors.forename: Nan-Hua
authors.initials: NH
authors.lastname: Chang
authors.affiliation: Krembil Research Institute, University Health Network, Toronto, Ontario M5T 2S8, Canada.|Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada; and.
authors.forename: Dario Michael
authors.initials: DM
authors.lastname: Ferri
authors.affiliation: Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada; and.
authors.forename: Thierry
authors.initials: T
authors.lastname: Mallevaey
authors.affiliation: Krembil Research Institute, University Health Network, Toronto, Ontario M5T 2S8, Canada; jwither@uhnres.utoronto.ca.|Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada; and.|Department of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors.forename: Joan E
authors.initials: JE
authors.lastname: Wither
mesh_terms: D000818:Animals; D055610:Antigens, CD1d / Q000276:immunology; D000950:Antigens, Ly / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism; D034741:RNA, Small Interfering; D000071176:Signaling Lymphocytic Activation Molecule Family / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D055610:Antigens, CD1d; D000950:Antigens, Ly; D016207:Cytokines; D034741:RNA, Small Interfering; D000071176:Signaling Lymphocytic Activation Molecule Family; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; C498972:Ly9 protein, mouse; C000604060:SLAMF6 protein, human; C000604062:Slamf1 protein, mouse; C000604063:Slamf6 protein, mouse