Interleukin 2 modulates thymic-derived regulatory T cell epigenetic landscape

• Published in: Nature communications Vol. 9; no. 1; pp. 5368 - 17
• Main Authors: Chorro, Laurent, Suzuki, Masako, Chin, Shu Shien, Williams, Tere M., Snapp, Erik L., Odagiu, Livia, Labrecque, Nathalie, Lauvau, Grégoire
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18-12-2018; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/106; 13/109; 38/15; 38/23; 38/39; 38/43; 38/61; 38/77; 38/91; 631/250/1619/554/1898/1271; 631/250/2152/569; 631/250/2502/2170; 631/250/38; Animals; Autoimmunity; Autoimmunity - genetics; CD4 antigen; Cell Differentiation - immunology; Cell lineage; Cellular Reprogramming - genetics; Cellular Reprogramming - immunology; Chromatin; Disease Models, Animal; Epigenesis, Genetic - immunology; Epigenetics; Female; Forkhead Transcription Factors - immunology; Forkhead Transcription Factors - metabolism; Foxp3 protein; Genomes; HEK293 Cells; Homeostasis; Humanities and Social Sciences; Humans; Interleukin 2; Interleukin-2 - immunology; Interleukin-2 - metabolism; Interleukin-2 Receptor alpha Subunit - genetics; Interleukin-2 Receptor alpha Subunit - immunology; Interleukin-2 Receptor alpha Subunit - metabolism; Listeriosis - immunology; Listeriosis - microbiology; Lymphocytes; Lymphocytes T; Male; Matrix Attachment Region Binding Proteins - genetics; Matrix Attachment Region Binding Proteins - metabolism; Mice; Mice, Inbred C57BL; Mice, Transgenic; multidisciplinary; Science; Science (multidisciplinary); Signal Transduction - genetics; Signal Transduction - immunology; T cell receptors; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Thymocytes; Thymocytes - immunology; Thymocytes - metabolism; Thymocytes - physiology; Thymus; Thymus Gland - cytology
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-07806-6

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.
Regulatory T (Treg) cells are developed in the thymus, and are essential for suppressing detrimental autoimmunity. Here the authors show, using mice with dampened interleukin 2 (IL-2) signaling, that IL-2 helps position the pioneer factor SATB1 to control genome-wide chromatin accessibility to facilitate T
reg
cell lineage commitment in the thymus.