Interferon gamma mediates the reduction of adipose tissue regulatory T cells in human obesity

David Bradley, Alan J. Smith, Alecia Blaszczak, Dharti Shantaram, Stephen M. Bergin, Anahita Jalilvand, Valerie Wright, Kathleen L. Wyne, Revati S. Dewal, Lisa A. Baer, Katherine R. Wright, Kristin I. Stanford, Bradley Needleman, Stacy Brethauer, Sabrena Noria, David Renton, Joshua J. Joseph, Amy Lovett-Racke, Joey Liu, Willa A. Hsueh

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Decreased adipose tissue regulatory T cells contribute to insulin resistance in obese mice, however, little is known about the mechanisms regulating adipose tissue regulatory T cells numbers in humans. Here we obtain adipose tissue from obese and lean volunteers. Regulatory T cell abundance is lower in obese vs. lean visceral and subcutaneous adipose tissue and associates with reduced insulin sensitivity and altered adipocyte metabolic gene expression. Regulatory T cells numbers decline following high-fat diet induction in lean volunteers. We see alteration in major histocompatibility complex II pathway in adipocytes from obese patients and after high fat ingestion, which increases T helper 1 cell numbers and decreases regulatory T cell differentiation. We also observe increased expression of inhibitory co-receptors including programmed cell death protein 1 and OX40 in visceral adipose tissue regulatory T cells from patients with obesity. In human obesity, these global effects of interferon gamma to reduce regulatory T cells and diminish their function appear to instigate adipose inflammation and suppress adipocyte metabolism, leading to insulin resistance.

Original languageEnglish (US)
Article number5606
JournalNature communications
Volume13
Issue number1
DOIs
StatePublished - Dec 2022

All Science Journal Classification (ASJC) codes

  • General Physics and Astronomy
  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology

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