title: Regulation of adipose tissue T cell subsets by Stat3 is crucial for diet-induced obesity and insulin resistance.
abstract: Dysregulated inflammation in adipose tissue, marked by increased proinflammatory T-cell accumulation and reduced regulatory T cells (Tregs), contributes to obesity-associated insulin resistance. The molecular mechanisms underlying T-cell-mediated inflammation in adipose tissue remain largely unknown, however. Here we show a crucial role for signal transducer and activator of transcription 3 (Stat3) in T cells in skewing adaptive immunity in visceral adipose tissue (VAT), thereby contributing to diet-induced obesity (DIO) and insulin resistance. Stat3 activity is elevated in obese VAT and in VAT-resident T cells. Functional ablation of Stat3 in T cells reduces DIO, improves insulin sensitivity and glucose tolerance, and suppresses VAT inflammation. Importantly, Stat3 ablation reverses the high Th1/Treg ratio in VAT of DIO mice that is likely secondary to elevated IL-6 production, leading in turn to suppression of Tregs. In addition, Stat3 in T cells in DIO mice affects adipose tissue macrophage accumulation and M2 phenotype. Our study identifies Stat3 in VAT-resident T cells as an important mediator and direct target for regulating adipose tissue inflammation, DIO, and its associated metabolic dysfunctions.
authors.affiliation: Department of Cancer Immunotherapeutics and Tumor Immunology, Beckman Research Institute, Duarte, CA 91010, USA.
authors.forename: Saul J
authors.initials: SJ
authors.lastname: Priceman
authors.forename: Maciej
authors.initials: M
authors.lastname: Kujawski
authors.forename: Shudan
authors.initials: S
authors.lastname: Shen
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Cherryholmes
authors.forename: Heehyoung
authors.initials: H
authors.lastname: Lee
authors.forename: Chunyan
authors.initials: C
authors.lastname: Zhang
authors.forename: Laura
authors.initials: L
authors.lastname: Kruper
authors.forename: Joanne
authors.initials: J
authors.lastname: Mortimer
authors.forename: Richard
authors.initials: R
authors.lastname: Jove
authors.forename: Arthur D
authors.initials: AD
authors.lastname: Riggs
authors.forename: Hua
authors.initials: H
authors.lastname: Yu
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D059305:Diet, High-Fat / Q000009:adverse effects; D005215:Fasting / Q000097:blood; D005260:Female; D005434:Flow Cytometry; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D050152:Intra-Abdominal Fat / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000097:blood / Q000209:etiology / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007328:Insulin; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D007371:Interferon-gamma