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Protein SUMOylation is required for regulatory T cell expansion and function

ABSTRACT: Foxp3-expressing regulatory T (Treg) cells are essential regulators in the immune system; molecular mechanisms underlying Treg cell expansion and function are still not well understood. SUMOylation is an important post-translational modification characterized by covalent attachment of SUMO moieties to lysine within proteins. UBC9 is the only E2 conjugation enzyme involved in this process and loss of UBC9 completely impairs the SUMOylation pathway. Here we report that selective deletion ofÂ Ubc9Â within the Treg cell lineage resulted in fatal early-onset autoimmunity as the Foxp3 mutant mice. Ubc9-deficient Treg cells exhibited severe defects in TCR-driven homeostatic proliferation, accompanied by impaired activation and compromised suppressor function. Importantly, TCR-enhanced SUMOylation of IRF4, a critical regulator of Treg cell function downstream of TCR signals, regulates its stability in Treg cells. Our data thus have demonstrated an essential role of SUMOylation in the expansion and function of Treg cells. RNA-seq library was generated using mRNA of CD4+ YFP+ Treg cells sorted from lymph nodes and spleen of Foxp3cre/wtUbc9fl/wt or Foxp3cre/wtUbc9fl/fl mice, each sample contained pooled Treg cells from 5~10 mice.

ORGANISM(S): Mus musculus

SUBMITTER: Xiaopeng Ma

PROVIDER: E-GEOD-82031 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Protein SUMOylation is required for regulatory T cell expansion and function

Project description:Foxp3-expressing regulatory T (Treg) cells are essential regulators in the immune system; molecular mechanisms underlying Treg cell expansion and function are still not well understood. SUMOylation is an important post-translational modification characterized by covalent attachment of SUMO moieties to lysine within proteins. UBC9 is the only E2 conjugation enzyme involved in this process and loss of UBC9 completely impairs the SUMOylation pathway. Here we report that selective deletion of Ubc9 within the Treg cell lineage resulted in fatal early-onset autoimmunity as the Foxp3 mutant mice. Ubc9-deficient Treg cells exhibited severe defects in TCR-driven homeostatic proliferation, accompanied by impaired activation and compromised suppressor function. Importantly, TCR-enhanced SUMOylation of IRF4, a critical regulator of Treg cell function downstream of TCR signals, regulates its stability in Treg cells. Our data thus have demonstrated an essential role of SUMOylation in the expansion and function of Treg cells.

2016-05-31 | GSE82031 | GEO

Inhibition of p300 impairs Foxp3+ T-regulatory cell function and promotes anti-tumor immunity

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Two Histone/Protein Acetyltransferases, CBP and p300, Are Indispensable for Foxp3+ T-regulatory Cell Development and Function

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2014-08-12 | E-GEOD-60318 | biostudies-arrayexpress

Next Generation Sequencing Facilitates Quantitative Analysis of Wild Type and poh1-/- splenic foxp3＋Treg cells

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2020-12-12 | GSE110084 | GEO

Non-classical action of Ku70 promotes Treg suppressive function through a FOXP3-dependent mechanism in lung adenocarcinoma

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Tregs from Bcl11b-deficient versus wild type Tregs (CD4Cre and Foxp3Cre systems)

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2019-09-02 | PXD011164 | Pride

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Project description:Foxp3+ regulatory T cells (Treg cells) maintain immunological tolerance and their deficiency results in fatal multi-organ autoimmunity. Although heightened T cell receptor (TCR) signaling is critical for the differentiation of Treg cells, the role of TCR signaling in Treg cell function remains largely unknown. Here we demonstrate inducible ablation of the TCR results in Treg cell dysfunction which cannot be attributed to impaired Foxp3 expression, decreased expression of Treg cell signature genes or altered ability to sense and consume interleukin 2. Rather, TCR signaling was required for maintaining the expression of a limited subset of genes comprising 25% of the activated Treg cell transcriptional signature. Our results reveal a critical role for the TCR in Treg cell suppressor capacity. Array expression of Foxp3-CreERT2 CalphaFL/WT mice

2014-09-08 | E-GEOD-61077 | biostudies-arrayexpress

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