An OGT-STAT5 Axis in Regulatory T Cells Controls Energy and Iron Metabolism

Zengdi Zhang, Oscar C. Salgado, Bing Liu, Zahra Moazzami, Kristin A. Hogquist, Michael A. Farrar, Hai Bin Ruan

Research output: Contribution to journalArticlepeer-review

Abstract

The immunosuppressive regulatory T (Treg) cells exert emerging effects on adipose tissue homeostasis and systemic metabolism. However, the metabolic regulation and effector mechanisms of Treg cells in coping with obesogenic insults are not fully understood. We have previously established an indispensable role of the O-linked N-Acetylglucosamine (O-GlcNAc) signaling in maintaining Treg cell identity and promoting Treg suppressor function, via STAT5 O-GlcNAcylation and activation. Here, we investigate the O-GlcNAc transferase (OGT)-STAT5 axis in driving the immunomodulatory function of Treg cells for metabolic homeostasis. Treg cell-specific OGT deficiency renders mice more vulnerable to high-fat diet (HFD)-induced adiposity and insulin resistance. Conversely, constitutive STAT5 activation in Treg cells confers protection against adipose tissue expansion and impaired glucose and insulin metabolism upon HFD feeding, in part by suppressing adipose lipid uptake and redistributing systemic iron storage. Treg cell function can be augmented by targeting the OGT-STAT5 axis to combat obesity and related metabolic disorders.

Original languageEnglish (US)
Article number874863
JournalFrontiers in immunology
Volume13
DOIs
StatePublished - Jul 8 2022

Bibliographical note

Funding Information:
This work was supported by NIH grant R56 AI162791 to H-BR and R01 AI139420 to H-BR and MF.

Publisher Copyright:
Copyright © 2022 Zhang, Salgado, Liu, Moazzami, Hogquist, Farrar and Ruan.

Keywords

  • O-GlcNAc
  • Treg - regulatory T cell
  • adipose tissue
  • fatty acid uptake
  • iron

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

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