ResearchIn-Press PreviewEndocrinologyImmunology
Open Access | 10.1172/jci.insight.140644
1Department of Immunology, University of Pittsburgh, Pittsburgh, United States of America
2Division of Endocrinology, University of Pittsburgh, Pittsburgh, United States of America
3Center for Biologic Imaging, University of Pittsburgh, Pittsburgh, United States of America
4Department of Pediatrics, University of Pittsburgh, Pittsburgh, United States of America
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1Department of Immunology, University of Pittsburgh, Pittsburgh, United States of America
2Division of Endocrinology, University of Pittsburgh, Pittsburgh, United States of America
3Center for Biologic Imaging, University of Pittsburgh, Pittsburgh, United States of America
4Department of Pediatrics, University of Pittsburgh, Pittsburgh, United States of America
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1Department of Immunology, University of Pittsburgh, Pittsburgh, United States of America
2Division of Endocrinology, University of Pittsburgh, Pittsburgh, United States of America
3Center for Biologic Imaging, University of Pittsburgh, Pittsburgh, United States of America
4Department of Pediatrics, University of Pittsburgh, Pittsburgh, United States of America
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1Department of Immunology, University of Pittsburgh, Pittsburgh, United States of America
2Division of Endocrinology, University of Pittsburgh, Pittsburgh, United States of America
3Center for Biologic Imaging, University of Pittsburgh, Pittsburgh, United States of America
4Department of Pediatrics, University of Pittsburgh, Pittsburgh, United States of America
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1Department of Immunology, University of Pittsburgh, Pittsburgh, United States of America
2Division of Endocrinology, University of Pittsburgh, Pittsburgh, United States of America
3Center for Biologic Imaging, University of Pittsburgh, Pittsburgh, United States of America
4Department of Pediatrics, University of Pittsburgh, Pittsburgh, United States of America
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1Department of Immunology, University of Pittsburgh, Pittsburgh, United States of America
2Division of Endocrinology, University of Pittsburgh, Pittsburgh, United States of America
3Center for Biologic Imaging, University of Pittsburgh, Pittsburgh, United States of America
4Department of Pediatrics, University of Pittsburgh, Pittsburgh, United States of America
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1Department of Immunology, University of Pittsburgh, Pittsburgh, United States of America
2Division of Endocrinology, University of Pittsburgh, Pittsburgh, United States of America
3Center for Biologic Imaging, University of Pittsburgh, Pittsburgh, United States of America
4Department of Pediatrics, University of Pittsburgh, Pittsburgh, United States of America
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1Department of Immunology, University of Pittsburgh, Pittsburgh, United States of America
2Division of Endocrinology, University of Pittsburgh, Pittsburgh, United States of America
3Center for Biologic Imaging, University of Pittsburgh, Pittsburgh, United States of America
4Department of Pediatrics, University of Pittsburgh, Pittsburgh, United States of America
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1Department of Immunology, University of Pittsburgh, Pittsburgh, United States of America
2Division of Endocrinology, University of Pittsburgh, Pittsburgh, United States of America
3Center for Biologic Imaging, University of Pittsburgh, Pittsburgh, United States of America
4Department of Pediatrics, University of Pittsburgh, Pittsburgh, United States of America
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1Department of Immunology, University of Pittsburgh, Pittsburgh, United States of America
2Division of Endocrinology, University of Pittsburgh, Pittsburgh, United States of America
3Center for Biologic Imaging, University of Pittsburgh, Pittsburgh, United States of America
4Department of Pediatrics, University of Pittsburgh, Pittsburgh, United States of America
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1Department of Immunology, University of Pittsburgh, Pittsburgh, United States of America
2Division of Endocrinology, University of Pittsburgh, Pittsburgh, United States of America
3Center for Biologic Imaging, University of Pittsburgh, Pittsburgh, United States of America
4Department of Pediatrics, University of Pittsburgh, Pittsburgh, United States of America
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1Department of Immunology, University of Pittsburgh, Pittsburgh, United States of America
2Division of Endocrinology, University of Pittsburgh, Pittsburgh, United States of America
3Center for Biologic Imaging, University of Pittsburgh, Pittsburgh, United States of America
4Department of Pediatrics, University of Pittsburgh, Pittsburgh, United States of America
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1Department of Immunology, University of Pittsburgh, Pittsburgh, United States of America
2Division of Endocrinology, University of Pittsburgh, Pittsburgh, United States of America
3Center for Biologic Imaging, University of Pittsburgh, Pittsburgh, United States of America
4Department of Pediatrics, University of Pittsburgh, Pittsburgh, United States of America
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1Department of Immunology, University of Pittsburgh, Pittsburgh, United States of America
2Division of Endocrinology, University of Pittsburgh, Pittsburgh, United States of America
3Center for Biologic Imaging, University of Pittsburgh, Pittsburgh, United States of America
4Department of Pediatrics, University of Pittsburgh, Pittsburgh, United States of America
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1Department of Immunology, University of Pittsburgh, Pittsburgh, United States of America
2Division of Endocrinology, University of Pittsburgh, Pittsburgh, United States of America
3Center for Biologic Imaging, University of Pittsburgh, Pittsburgh, United States of America
4Department of Pediatrics, University of Pittsburgh, Pittsburgh, United States of America
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1Department of Immunology, University of Pittsburgh, Pittsburgh, United States of America
2Division of Endocrinology, University of Pittsburgh, Pittsburgh, United States of America
3Center for Biologic Imaging, University of Pittsburgh, Pittsburgh, United States of America
4Department of Pediatrics, University of Pittsburgh, Pittsburgh, United States of America
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Published December 22, 2020 - More info
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 significant 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 (HFD)-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-1-deficient mice were protected from glucose intolerance, insulin resistance and diet-induced obesity (DIO), 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.