Interleukin 2 modulates thymic-derived regulatory T cell epigenetic landscape

Laurent Chorro, Masako Suzuki, Shu Shien Chin, Tere M. Williams, Erik L. Snapp, Livia Odagiu, Nathalie Labrecque, Gregoire Lauvau

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Foxp3+CD4+ regulatory T (Treg) cells are essential for preventing fatal autoimmunity and safeguard immune homeostasis in vivo. While expression of the transcription factor Foxp3 and IL-2 signals are both required for the development and function of Treg cells, the commitment to the Treg cell lineage occurs during thymic selection upon T cell receptor (TCR) triggering, and precedes the expression of Foxp3. Whether signals beside TCR contribute to establish Treg cell epigenetic and functional identity is still unknown. Here, using a mouse model with reduced IL-2 signaling, we show that IL-2 regulates the positioning of the pioneer factor SATB1 in CD4+ thymocytes and controls genome wide chromatin accessibility of thymic-derived Treg cells. We also show that Treg cells receiving only low IL-2 signals can suppress endogenous but not WT autoreactive T cell responses in vitro and in vivo. Our findings have broad implications for potential therapeutic strategies to reprogram Treg cells in vivo.

Original languageEnglish (US)
Article number5368
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

Fingerprint

interleukins
T-cells
Regulatory T-Lymphocytes
Epigenomics
Interleukin-2
T-Cell Antigen Receptor
cells
Chromatin
Transcription Factors
Genes
homeostasis
chromatin
genome
Cell Lineage
Thymocytes
positioning
mice
Autoimmunity
Homeostasis
Genome

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Interleukin 2 modulates thymic-derived regulatory T cell epigenetic landscape. / Chorro, Laurent; Suzuki, Masako; Chin, Shu Shien; Williams, Tere M.; Snapp, Erik L.; Odagiu, Livia; Labrecque, Nathalie; Lauvau, Gregoire.

In: Nature Communications, Vol. 9, No. 1, 5368, 01.12.2018.

Research output: Contribution to journalArticle

Chorro, Laurent ; Suzuki, Masako ; Chin, Shu Shien ; Williams, Tere M. ; Snapp, Erik L. ; Odagiu, Livia ; Labrecque, Nathalie ; Lauvau, Gregoire. / Interleukin 2 modulates thymic-derived regulatory T cell epigenetic landscape. In: Nature Communications. 2018 ; Vol. 9, No. 1.
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