The lineage stability and suppressive program of regulatory T cells require protein O-GlcNAcylation

Bing Liu, Oscar C. Salgado, Sangya Singh, Keli L Hippen, Jason C. Maynard, Alma L. Burlingame, Lauren E. Ball, Bruce R Blazar, Michael A Farrar, Kristin A Hogquist, Hai-Bin Ruan

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Regulatory T (Treg) cells control self-tolerance, inflammatory responses and tissue homeostasis. In mature Treg cells, continued expression of FOXP3 maintains lineage identity, while T cell receptor (TCR) signaling and interleukin-2 (IL-2)/STAT5 activation support the suppressive effector function of Treg cells, but how these regulators synergize to control Treg cell homeostasis and function remains unclear. Here we show that TCR-activated posttranslational modification by O-linked N-Acetylglucosamine (O-GlcNAc) stabilizes FOXP3 and activates STAT5, thus integrating these critical signaling pathways. O-GlcNAc-deficient Treg cells develop normally but display modestly reduced FOXP3 expression, strongly impaired lineage stability and effector function, and ultimately fatal autoimmunity in mice. Moreover, deficiency in protein O-GlcNAcylation attenuates IL-2/STAT5 signaling, while overexpression of a constitutively active form of STAT5 partially ameliorates Treg cell dysfunction and systemic inflammation in O-GlcNAc deficient mice. Collectively, our data demonstrate that protein O-GlcNAcylation is essential for lineage stability and effector function in Treg cells.

Original languageEnglish (US)
Article number354
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

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T-cells
Regulatory T-Lymphocytes
proteins
effectors
T-Cell Antigen Receptor
cells
Interleukin-2
Tissue homeostasis
Proteins
interleukins
homeostasis
Acetylglucosamine
mice
Homeostasis
Chemical activation
Self Tolerance
regulators
Protein Deficiency
Critical Pathways
Post Translational Protein Processing

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

Cite this

The lineage stability and suppressive program of regulatory T cells require protein O-GlcNAcylation. / Liu, Bing; Salgado, Oscar C.; Singh, Sangya; Hippen, Keli L; Maynard, Jason C.; Burlingame, Alma L.; Ball, Lauren E.; Blazar, Bruce R; Farrar, Michael A; Hogquist, Kristin A; Ruan, Hai-Bin.

In: Nature communications, Vol. 10, No. 1, 354, 01.12.2019.

Research output: Contribution to journalArticle

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AU - Burlingame, Alma L.

AU - Ball, Lauren E.

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AU - Ruan, Hai-Bin

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