Regulatory T cells control Effector T cell Inflammation in Human Prediabetes
Name
db210659.pdf
Description
Published version
Size
1.07 MB
Format
Adobe PDF
Checksum (MD5)
e23138b0f229dbe9d4cd095ebad4b352
Author(s)
Liu, Rui
Pugh, Gabriella H
Tevonian, Erin
Thompson, Katherine
Lauffenburger, Douglas A
Kern, Philip A
Nikolajczyk, Barbara S
Date Issued
2022
Journal
Diabetes
Publisher
American Diabetes Association
Citation
Liu, Rui, Pugh, Gabriella H, Tevonian, Erin, Thompson, Katherine, Lauffenburger, Douglas A et al. 2022. "Regulatory T cells control Effector T cell Inflammation in Human Prediabetes." Diabetes, 71 (2).
Version
Final published version
Abstract
A disparate array of plasma/serum markers provides evidence for chronic inflammation in human prediabetes, a condition that is most closely replicated by standard mouse models of obesity and metaflammation. These remain largely nonactionable 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 (Treg) control mitochondrial function and cytokine production by CD4+ effector T cells (Teff) in prediabetes and type 2 diabetes by supporting T helper (Th)17 or Th1 cytokine production, respectively. These data suggest that Treg control of Teff metabolism regulates inflammation differentially in prediabetes compared with type 2 diabetes. Queries of genes that impact mitochondrial function or pathways leading to transcription of lipid metabolism genes identified the fatty acid importer CD36 as highly expressed in Treg but not Teff from subjects with prediabetes. Pharmacological blockade of CD36 in Treg from subjects with prediabetes decreased Teff production of the Th17 cytokines that differentiate overall prediabetes inflammation. We conclude that Treg 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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.2337/DB21-0659
