期刊
JCI INSIGHT
卷 6, 期 3, 页码 -出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/jci.insight.140644
关键词
-
资金
- NIH [R01 DK114012, R01 DK119627, 5T32AI089443-11]
- Center for Metabolism and Mitochondrial Medicine by the Pittsburgh Foundation [MR2020 109502]
- University of Pittsburgh
IL-10, produced by CD4(+)Foxp3(+) regulatory T cells, can suppress adipocyte beiging, leading to reduced insulin resistance and obesity. Loss of IL-10 in Tregs, through the transcription factor Blimp-1, resulted in improved metabolic outcomes in high-fat diet-fed mice. This highlights the important role of Treg-derived IL-10 in regulating adipose tissue homeostasis.
Interleukin-10 (IL-10) is a critical cytokine used by immune cells to suppress inflammation. Paradoxically, immune cell-derived IL-10 can drive insulin resistance in obesity by suppressing adipocyte energy expenditure and thermogenesis. However, the source of IL-10 necessary for the suppression of adipocyte thermogenesis is unknown. We show here that CD4(+)Foxp3(+) regulatory T cells (Tregs) are a substantial source of IL-10 and that Treg-derived IL-10 can suppress adipocyte beiging. Unexpectedly, Treg-specific loss of IL-10 resulted in increased insulin sensitivity and reduced obesity in high-fat diet-fed male mice. Mechanistically, we determined that Treg-specific loss of the transcription factor Blimp-1, a driver of IL-10 expression by Tregs, phenocopied the Treg-specific IL-10-deficient mice. Loss of Blimp-1 expression in Tregs resulted in reduced ST2(+)KLRG1(+), IL-10-secreting Tregs, particularly in the white adipose tissue. Blimp-l-deficient mice were protected from glucose intolerance, insulin resistance, and diet-induced obesity, through increased white adipose tissue browning. Taken together, our data show that Blimp-1-regulated IL-10 secretion by Tregs represses white adipose tissue beiging to maintain adipose tissue homeostasis.
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