The Nuclear Receptor Nr4a1 Controls CD8 T Cell Development Through Transcriptional Suppression of Runx3

• Published in: Scientific reports Vol. 5; no. 1; p. 9059
• Main Authors: Nowyhed, Heba N., Huynh, Tridu R., Blatchley, Amy, Wu, Runpei, Thomas, Graham D., Hedrick, Catherine C.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.03.2015; Nature Publishing Group
• Subjects: 13/106; 13/109; 13/2; 13/31; 13/44; 38/77; 38/90; 631/250; 631/250/2502; Adoptive Transfer; Animals; CD8 antigen; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell Differentiation; Core Binding Factor Alpha 3 Subunit - genetics; Down-Regulation; Gene Expression Regulation; Humanities and Social Sciences; Lymphocyte Count; Lymphocytes; Lymphocytes T; Mice; Mice, Knockout; multidisciplinary; Nerve Tissue Proteins - metabolism; Nuclear Receptor Subfamily 4, Group A, Member 1 - genetics; Nuclear Receptor Subfamily 4, Group A, Member 1 - metabolism; Protein Binding; Repressor Proteins - metabolism; Runx3 protein; Science; Thymocytes; Thymus; Thymus Gland - cytology; Thymus Gland - immunology; Transcription; Transcription, Genetic; Transplantation Chimera
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep09059

The NR4A nuclear receptor family member Nr4a1 is strongly induced in thymocytes undergoing selection and has been shown to control the development of T reg cells; however the role of Nr4a1 in CD8 + T cells remains undefined. Here we report a novel role for Nr4a1 in regulating the development and frequency of CD8 + T cells through direct transcriptional control of Runx3 . We discovered that Nr4a1 recruits the corepressor, CoREST to suppress Runx3 expression in CD8 + T cells. Loss of Nr4a1 results in increased Runx3 expression in thymocytes which consequently causes a 2-fold increase in the frequency and total number of intrathymic and peripheral CD8 + T cells. Our findings establish Nr4a1 as a novel and critical player in the regulation of CD8 T cell development through the direct suppression of Runx3 .