title: Interleukin-13 Pathway Alterations Impair Invariant Natural Killer T-Cell-Mediated Regulation of Effector T Cells in Type 1 Diabetes.
abstract: Many studies have shown that human natural killer T (NKT) cells can promote immunity to pathogens, but their regulatory function is still being investigated. Invariant NKT (iNKT) cells have been shown to be effective in preventing type 1 diabetes in the NOD mouse model. Activation of plasmacytoid dendritic cells, modulation of B-cell responses, and immune deviation were proposed to be responsible for the suppressive effect of iNKT cells. We studied the regulatory capacity of human iNKT cells from control subjects and patients with type 1 diabetes (T1D) at disease clinical onset. We demonstrate that control iNKT cells suppress the proliferation of effector T cells (Teffs) through a cell contact-independent mechanism. Of note, suppression depended on the secretion of interleukin-13 (IL-13) by iNKT cells because an antibody blocking this cytokine resulted from the abrogation of Teff suppression; however, T1D-derived iNKT cells showed impaired regulation that could be attributed to the decrease in IL-13 secretion. Thus, alteration of the IL-13 pathway at disease onset may lead to the progression of the autoimmune response in T1D. Advances in the study of iNKT cells and the selection of agonists potentiating IL-13 secretion should permit new therapeutic strategies to prevent the development of T1D.
authors.affiliation: Immunology Unit, Institut de Biotecnologia i Biomedicina, and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Lorena
authors.initials: L
authors.lastname: Usero
authors.affiliation: Immunology Unit, Institut de Biotecnologia i Biomedicina, and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Sánchez
authors.affiliation: Unitat d'Endocrinologia, Hospital de Mataró, Barcelona, Spain.
authors.forename: Eduarda
authors.initials: E
authors.lastname: Pizarro
authors.affiliation: Immunology Unit, Institut de Biotecnologia i Biomedicina, and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Xufré
authors.affiliation: Immunology Unit, Institut de Biotecnologia i Biomedicina, and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Mercè
authors.initials: M
authors.lastname: Martí
authors.affiliation: Immunology Unit, Institut de Biotecnologia i Biomedicina, and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Dolores
authors.identifier: 0000-0003-3328-740X
authors.initials: D
authors.lastname: Jaraquemada
authors.affiliation: Immunology Unit, Institut de Biotecnologia i Biomedicina, and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Barcelona, Spain carme.roura@uab.cat.
authors.forename: Carme
authors.initials: C
authors.lastname: Roura-Mir
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D018793:Interleukin-13 / Q000378:metabolism*; D008297:Male; D016688:Mice, Inbred NOD; D008875:Middle Aged; D055611:Natural Killer T-Cells / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism; D055815:Young Adult
chemical_list: D016207:Cytokines; D018793:Interleukin-13