American Diabetes Association
Final Suppl Figs 11.16.21_v2.pdf (843.92 kB)

Regulatory T cells control Effector T cell Inflammation in Human Prediabetes

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Version 2 2022-01-06, 19:05
Version 1 2021-11-04, 15:09
posted on 2022-01-06, 19:05 authored by Rui Liu, Gabriella H. Pugh, Erin Tevonian, Katherine Thompson, Douglas A. Lauffenburger, Philip A. Kern, Barbara S. Nikolajczyk
A disparate array of plasma/serum markers provide evidence for chronic inflammation in human prediabetes, a condition that is most closely replicated by standard mouse models of obesity and meta-flammation. These remain largely non-actionable, and contrast with our rich understanding of inflammation in human type 2 diabetes. New data show that inflammatory profiles produced by CD4+ T cells define human prediabetes as a unique inflammatory state. Regulatory T cells (Tregs) control mitochondrial function and cytokine production by CD4+ effector T cells (Teff) in prediabetes and type 2 diabetes by supporting Th17 or Th1 cytokine production, respectively. These data suggest that Treg control of Teff metabolism controls inflammation differentially in prediabetes compared to type 2 diabetes. Queries of genes that impact mitochondrial function and/or pathways leading to transcription of lipid metabolism genes identified the fatty acid importer CD36 as highly expressed in Tregs but not Teff from prediabetes subjects. Pharmacological blockade of CD36 in Tregs from prediabetes subjects decreased Teff production of the Th17 cytokines that differentiate overall prediabetes inflammation. We conclude Tregs control CD4+ T cell cytokine profiles through mechanisms determined, at least in part, by host metabolic status. Furthermore, Treg CD36 uniquely promotes Th17 cytokine production by Teff in prediabetes.


This work was funded by R01DK108056 (BSN, PAK and DAL) the University of Kentucky Pharmaceutical Sciences PhD Program (RL), the Shared Resource Facility of the University of Kentucky Markey Cancer Center P30 CA 177558, Barnstable Brown Diabetes and Obesity Center (BSN), NIH National Center for Advancing Translational Sciences UL1TR001998 (PAK) and the Army Institute for Collaborative Biotechnologies Cooperative Agreement W911NF-19-2-0026 from the Army Research Office (DAL).


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