title: Altered distribution and increased IL-17 production by mucosal-associated invariant T cells in adult and childhood obesity.
abstract: Mucosal-associated invariant T (MAIT) cells are innate MHC-unrestricted cells that regulate inflammatory responses through the rapid production of cytokines. In this article, we show that circulating MAIT cells are depleted in obese adults, and depletion is associated with diabetic status. Circulating MAIT cells more frequently produced IL-17 upon stimulation ex vivo, a cytokine implicated in insulin resistance. MAIT cells were enriched in adipose tissue (AT) compared with blood. AT MAIT cells, but not circulating MAIT cells, were capable of producing IL-10. In AT from obese subjects, MAIT cells were depleted, were less likely to produce IL-10, and more frequently produced IL-17. Finally, we show that IL-17(+) MAIT cells are also increased in childhood obesity, and altered MAIT cell frequencies in obese children are positively associated with insulin resistance. These data indicate that MAIT cells are enriched in human AT and display an IL-17(+) phenotype in both obese adults and children, correlating with levels of insulin resistance. The alterations in MAIT cells may be contributing to obesity-related sterile inflammation and insulin resistance.
authors.affiliation: Obesity Immunology Research, St Vincent's University Hospital and University College Dublin, Dublin 4, Ireland; National Children's Research Centre, Crumlin Children's Hospital, Dublin 12, Ireland;
authors.forename: Eirin
authors.initials: E
authors.lastname: Carolan
authors.affiliation: Obesity Immunology Research, St Vincent's University Hospital and University College Dublin, Dublin 4, Ireland;
authors.forename: Laura M
authors.initials: LM
authors.lastname: Tobin
authors.affiliation: Discipline of Immunology, School of Medicine, Trinity College Dublin, Dublin 8, Ireland;
authors.forename: Bozgana A
authors.initials: BA
authors.lastname: Mangan
authors.affiliation: Obesity Immunology Research, St Vincent's University Hospital and University College Dublin, Dublin 4, Ireland;
authors.forename: Michelle
authors.initials: M
authors.lastname: Corrigan
authors.affiliation: Obesity Immunology Research, St Vincent's University Hospital and University College Dublin, Dublin 4, Ireland;
authors.forename: Gadinthsware
authors.initials: G
authors.lastname: Gaoatswe
authors.affiliation: School of Biological Sciences, Dublin Institute of Technology, Dublin 2, Ireland;
authors.forename: Greg
authors.initials: G
authors.lastname: Byrne
authors.affiliation: Obesity Immunology Research, St Vincent's University Hospital and University College Dublin, Dublin 4, Ireland;
authors.forename: Justin
authors.initials: J
authors.lastname: Geoghegan
authors.affiliation: Department of Endocrinology, Our Ladies Children's Hospital Crumlin, Dublin 12, Ireland; and.
authors.forename: Declan
authors.initials: D
authors.lastname: Cody
authors.affiliation: Obesity Immunology Research, St Vincent's University Hospital and University College Dublin, Dublin 4, Ireland;
authors.forename: Jean
authors.initials: J
authors.lastname: O'Connell
authors.affiliation: Obesity Immunology Research, St Vincent's University Hospital and University College Dublin, Dublin 4, Ireland;
authors.forename: Desmond C
authors.initials: DC
authors.lastname: Winter
authors.affiliation: Discipline of Immunology, School of Medicine, Trinity College Dublin, Dublin 8, Ireland;
authors.forename: Derek G
authors.initials: DG
authors.lastname: Doherty
authors.affiliation: Rheumatology, Allergy and Immunology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
authors.forename: Lydia
authors.initials: L
authors.lastname: Lynch
authors.affiliation: Obesity Immunology Research, St Vincent's University Hospital and University College Dublin, Dublin 4, Ireland;
authors.forename: Donal
authors.initials: D
authors.lastname: O'Shea
authors.affiliation: Obesity Immunology Research, St Vincent's University Hospital and University College Dublin, Dublin 4, Ireland; National Children's Research Centre, Crumlin Children's Hospital, Dublin 12, Ireland; Andrew.Hogan@ncrc.ie.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Hogan
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D016022:Case-Control Studies; D002648:Child; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000276:immunology* / Q000378:metabolism; D009765:Obesity / Q000276:immunology* / Q000378:metabolism*; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*
chemical_list: D016207:Cytokines; D020381:Interleukin-17