title: Regulatory iNKT cells lack expression of the transcription factor PLZF and control the homeostasis of T(reg) cells and macrophages in adipose tissue.
abstract: Invariant natural killer T cells (iNKT cells) are lipid-sensing innate T cells that are restricted by the antigen-presenting molecule CD1d and express the transcription factor PLZF. iNKT cells accumulate in adipose tissue, where they are anti-inflammatory, but the factors that contribute to their anti-inflammatory nature, as well as their targets in adipose tissue, are unknown. Here we found that iNKT cells in adipose tissue had a unique transcriptional program and produced interleukin 2 (IL-2) and IL-10. Unlike other iNKT cells, they lacked PLZF but expressed the transcription factor E4BP4, which controlled their IL-10 production. The adipose iNKT cells were a tissue-resident population that induced an anti-inflammatory phenotype in macrophages and, through the production of IL-2, controlled the number, proliferation and suppressor function of regulatory T cells (Treg cells) in adipose tissue. Thus, iNKT cells in adipose tissue are unique regulators of immunological homeostasis in this tissue.
authors.affiliation: Department of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.
authors.forename: Lydia
authors.initials: L
authors.lastname: Lynch
authors.affiliation: Department of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.
authors.forename: Xavier
authors.initials: X
authors.lastname: Michelet
authors.affiliation: Department of Pediatrics, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA.
authors.forename: Sai
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Brennan
authors.affiliation: Department of Microbiology and Immunology, Harvard Medical School, Boston, USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Moseman
authors.affiliation: Department of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.
authors.forename: Chantel
authors.initials: C
authors.lastname: Lester
authors.affiliation: School of Biosciences, University of Birmingham, Edgbaston, Birmingham, UK.
authors.forename: Gurdyal
authors.initials: G
authors.lastname: Besra
authors.affiliation: Trudeau Institute, Saranac Lake, New York, USA.
authors.forename: Emilie E
authors.initials: EE
authors.lastname: Vomhof-Dekrey
authors.affiliation: Trudeau Institute, Saranac Lake, New York, USA.
authors.forename: Mike
authors.initials: M
authors.lastname: Tighe
authors.affiliation: 1] Department of Microbiology &Immunology, Peter Doherty Institute, University of Melbourne, Parkville, Australia. [2] Australian Research Council Centre of Excellence for Advanced Molecular Imaging, University of Melbourne, Australia.
authors.forename: Hui-Fern
authors.initials: HF
authors.lastname: Koay
authors.affiliation: 1] Department of Microbiology &Immunology, Peter Doherty Institute, University of Melbourne, Parkville, Australia. [2] Australian Research Council Centre of Excellence for Advanced Molecular Imaging, University of Melbourne, Australia.
authors.forename: Dale I
authors.initials: DI
authors.lastname: Godfrey
authors.affiliation: Trudeau Institute, Saranac Lake, New York, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Leadbetter
authors.affiliation: 1] Department of Pediatrics, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA. [2] Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA.
authors.forename: Derek B
authors.initials: DB
authors.lastname: Sant'Angelo
authors.affiliation: Department of Microbiology and Immunology, Harvard Medical School, Boston, USA.
authors.forename: Ulrich
authors.initials: U
authors.lastname: von Andrian
authors.affiliation: Department of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Brenner
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000276:immunology*; D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000276:immunology; D048708:Cell Growth Processes / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006706:Homeostasis / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology; D051741:Kruppel-Like Transcription Factors / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D013047:Specific Pathogen-Free Organisms; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology / Q000378:metabolism*
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D007376:Interleukin-2; D051741:Kruppel-Like Transcription Factors; C497441:Nfil3 protein, mouse; D000075722:Promyelocytic Leukemia Zinc Finger Protein; C513267:Zbtb16 protein, mouse; D016753:Interleukin-10