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 and Willa A. Hsueh ()
Additional contact information
David Bradley: The Ohio State University Wexner Medical Center
Alan J. Smith: The Ohio State University Wexner Medical Center
Alecia Blaszczak: The Ohio State University Wexner Medical Center
Dharti Shantaram: The Ohio State University Wexner Medical Center
Stephen M. Bergin: The Ohio State University Wexner Medical Center
Anahita Jalilvand: The Ohio State University Wexner Medical Center
Valerie Wright: The Ohio State University Wexner Medical Center
Kathleen L. Wyne: The Ohio State University Wexner Medical Center
Revati S. Dewal: The Ohio State University Wexner Medical Center
Lisa A. Baer: The Ohio State University Wexner Medical Center
Katherine R. Wright: The Ohio State University Wexner Medical Center
Kristin I. Stanford: The Ohio State University Wexner Medical Center
Bradley Needleman: The Ohio State University Wexner Medical Center
Stacy Brethauer: The Ohio State University Wexner Medical Center
Sabrena Noria: The Ohio State University Wexner Medical Center
David Renton: The Ohio State University Wexner Medical Center
Joshua J. Joseph: The Ohio State University Wexner Medical Center
Amy Lovett-Racke: The Ohio State University Wexner Medical Center
Joey Liu: The Ohio State University Wexner Medical Center
Willa A. Hsueh: The Ohio State University Wexner Medical Center

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-33067-5

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