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

ABSTRACT: Obesity leads to a switch in subsets of CD4+ T cell in adipose tissue, characterized by an increase in IFN? 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 IFN? 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 IFN? production in Th1 cells, whereas HFD-fed IFN?R1?/? mice were more insulin sensitive and had similarly high levels of Tregs in adipose tissue as aMHCII?/? mice. We further show that IFN? 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. Obesity is associated with inflammation in adipose tissue, characterized by a shift in local T cell subsets. Here the authors show that loss of MHCII expression on adipocytes increases levels of immunosuppressive regulatory T cells in adipose tissue, which enhances insulin sensitivity.

SUBMITTER: Deng T

PROVIDER: S-EPMC5510177 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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