Scientific reports 2015-01-01

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

Heba N Nowyhed, Tridu R Huynh, Amy Blatchley, Runpei Wu, Graham D Thomas, Catherine C Hedrick

Index: Sci. Rep. 5 , 9059, (2015)

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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.