title: Depletion of fat-resident Treg cells prevents age-associated insulin resistance.
abstract: Age-associated insulin resistance (IR) and obesity-associated IR are two physiologically distinct forms of adult-onset diabetes. While macrophage-driven inflammation is a core driver of obesity-associated IR, the underlying mechanisms of the obesity-independent yet highly prevalent age-associated IR are largely unexplored. Here we show, using comparative adipo-immune profiling in mice, that fat-resident regulatory T cells, termed fTreg cells, accumulate in adipose tissue as a function of age, but not obesity. Supporting the existence of two distinct mechanisms underlying IR, mice deficient in fTreg cells are protected against age-associated IR, yet remain susceptible to obesity-associated IR and metabolic disease. By contrast, selective depletion of fTreg cells via anti-ST2 antibody treatment increases adipose tissue insulin sensitivity. These findings establish that distinct immune cell populations within adipose tissue underlie ageing- and obesity-associated IR, and implicate fTreg cells as adipo-immune drivers and potential therapeutic targets in the treatment of age-associated IR.
authors.affiliation: Immunobiology and Microbial Pathogenesis Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.|Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
authors.forename: Sagar P
authors.initials: SP
authors.lastname: Bapat
authors.affiliation: Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.|Graduate School of Medical Science and Engineering, KAIST 34141, South Korea.
authors.forename: Jae
authors.initials: J
authors.lastname: Myoung Suh
authors.affiliation: Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.|Department of Biotechnology, College of Life Sciences, Sejong University, Seoul 143-747, South Korea.
authors.forename: Sungsoon
authors.initials: S
authors.lastname: Fang
authors.affiliation: Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
authors.forename: Sihao
authors.initials: S
authors.lastname: Liu
authors.affiliation: Immunobiology and Microbial Pathogenesis Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Immunobiology and Microbial Pathogenesis Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
authors.forename: Albert
authors.initials: A
authors.lastname: Cheng
authors.affiliation: Immunobiology and Microbial Pathogenesis Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
authors.forename: Carmen
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Immunobiology and Microbial Pathogenesis Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
authors.forename: Yuqiong
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
authors.forename: Mathias
authors.initials: M
authors.lastname: LeBlanc
authors.affiliation: Storr Liver Centre, Westmead Millennium Institute, Sydney Medical School, University of Sydney, Sydney 2145, Australia.
authors.forename: Christopher
authors.initials: C
authors.lastname: Liddle
authors.affiliation: Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
authors.forename: Annette R
authors.initials: AR
authors.lastname: Atkins
authors.affiliation: Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
authors.forename: Ruth T
authors.initials: RT
authors.lastname: Yu
authors.affiliation: Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Downes
authors.affiliation: Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.|Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Evans
authors.affiliation: Immunobiology and Microbial Pathogenesis Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zheng
mesh_terms: D000273:Adipose Tissue / Q000166:cytology* / Q000276:immunology*; D000375:Aging / Q000276:immunology*; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D007333:Insulin Resistance / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D008297:Male; D024821:Metabolic Syndrome / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009765:Obesity / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology*
chemical_list: D005947:Glucose