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, Grégoire Lauvau

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Foxp3 + CD4 + regulatory T (T reg ) 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 T reg cells, the commitment to the T reg 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 T reg 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 T reg cells. We also show that T reg 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 T reg cells in vivo.

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

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ASJC Scopus subject areas

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

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