The nuclear receptor nr4a1 controls CD8 T cell development through transcriptional suppression of runx3

Scientific Reports
Heba N NowyhedCatherine C Hedrick

Abstract

The NR4A nuclear receptor family member Nr4a1 is strongly induced in thymocytes undergoing selection, and has been shown to control the development of Treg 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.

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Citations

Jan 6, 2017·Expert Opinion on Therapeutic Targets·Ricardo Rodríguez-CalvoManuel Vázquez-Carrera
Oct 14, 2017·Nuclear Receptor Research·Brandon PraslickaChris R Gissendanner
May 1, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nabil ZeidanVibhuti P Dave
Sep 13, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Heba N NowyhedCatherine C Hedrick
Jun 10, 2018·Leukemia·Seth P BoudreauxOrla M Conneely
Dec 12, 2019·Immunological Medicine·Makoto AndoAkihiko Yoshimura
Oct 17, 2020·European Journal of Immunology·Sanne C LithCarlie J M de Vries
Dec 18, 2020·Frontiers in Pharmacology·Chenyang ZhangXiaobo Sun
Feb 17, 2021·Cell Death & Disease·Bojana JakicNatascha Hermann-Kleiter
Feb 19, 2021·Frontiers in Endocrinology·Livia OdagiuNathalie Labrecque
Jul 28, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Salix BouletNathalie Labrecque

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Methods Mentioned

BETA
transgenic
immunoprecipitation
transfection
Co-IP
PCR
flow cytometry
immunoprecipitation assay
ChIP
Assay

Software Mentioned

FlowJo
TreeStar

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