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

Tuo Deng, Joey Liu, Yanru Deng, Laurie J. 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, Willa A. Hsueh

Research output: Contribution to journalArticle

31 Scopus citations

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.

Original languageEnglish (US)
Article number15725
JournalNature Communications
Volume8
DOIs
StatePublished - Jul 12 2017

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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