Adipocyte adaptive immunity mediates diet-induced adipose inflammation and insulin resistance by decreasing adipose Treg cells

Tuo Deng (), Joey Liu, Yanru Deng, Laurie Minze, Xiang Xiao, Valerie Wright, Richeng Yu, Xian C. Li, Alecia Blaszczak, Stephen Bergin, David DiSilvestro, Ryan Judd, David Bradley, Michael Caligiuri, Christopher J. Lyon and Willa A. Hsueh ()
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Tuo Deng: Center for Bioenergetics, Houston Methodist Research Institute, Weill Cornell Medical College
Joey Liu: The Diabetes and Metabolism Research Center, Diabetes and Metabolism, The Ohio State University
Yanru Deng: Center for Bioenergetics, Houston Methodist Research Institute, Weill Cornell Medical College
Laurie Minze: Immunobiology and Transplantation Research, Houston Methodist Research Institute, Texas Medical Center
Xiang Xiao: Immunobiology and Transplantation Research, Houston Methodist Research Institute, Texas Medical Center
Valerie Wright: The Diabetes and Metabolism Research Center, Diabetes and Metabolism, The Ohio State University
Richeng Yu: Center for Bioenergetics, Houston Methodist Research Institute, Weill Cornell Medical College
Xian C. Li: Immunobiology and Transplantation Research, Houston Methodist Research Institute, Texas Medical Center
Alecia Blaszczak: The Diabetes and Metabolism Research Center, Diabetes and Metabolism, The Ohio State University
Stephen Bergin: The Comprehensive Cancer Center–Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University
David DiSilvestro: The Diabetes and Metabolism Research Center, Diabetes and Metabolism, The Ohio State University
Ryan Judd: Medical Scientist Training Program and Biomedical Sciences Graduate Program, The Ohio State University
David Bradley: The Diabetes and Metabolism Research Center, Diabetes and Metabolism, The Ohio State University
Michael Caligiuri: Medical Scientist Training Program and Biomedical Sciences Graduate Program, The Ohio State University
Christopher J. Lyon: Center for Bioenergetics, Houston Methodist Research Institute, Weill Cornell Medical College
Willa A. Hsueh: The Diabetes and Metabolism Research Center, Diabetes and Metabolism, The Ohio State University

Nature Communications, 2017, vol. 8, issue 1, 1-11

Abstract: Abstract Obesity leads to a switch in subsets of CD4+ T cell in adipose tissue, characterized by an increase in IFNγ producing Th1 cells and a decrease in anti-inflammatory regulatory T (Treg) cells, which impairs systemic insulin sensitivity. What signals these changes is unknown. Herein we demonstrate that genetic deficiency of adipocyte MHCII decreases adipose IFNγ expression and increases adipose Treg abundance in obese mice, leading to reduced obesity-induced adipose inflammation and reduced insulin resistance without affecting weight gain. The preserved insulin sensitivity of high fat diet (HFD)-fed adipocyte-specific MHCII knockout (aMHCII−/−) mice was substantially attenuated by adipose-specific Treg ablation. Adipocytes of aMHCII−/− mice exhibit decreased capacity to stimulate IFNγ production in Th1 cells, whereas HFD-fed IFNγR1−/− mice were more insulin sensitive and had similarly high levels of Tregs in adipose tissue as aMHCII−/− mice. We further show that IFNγ strongly inhibits IL-33 effects to promote adipose Treg proliferation. Our results identify MHCII in adipocyte as a critical determinant of the obesity-induced adipose T cell subset switch and insulin resistance.

Date: 2017
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DOI: 10.1038/ncomms15725

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