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

Heba N Nowyhed1, Tridu R Huynh1, Amy Blatchley1

  • 1Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA.

Scientific Reports
|March 13, 2015
PubMed

Insights

Nuclear receptor Nr4a1 regulates CD8(+) T cell development by suppressing Runx3 expression. Loss of Nr4a1 increases Runx3, leading to a twofold rise in CD8(+) T cell numbers.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cellular Biology

Background:

  • The nuclear receptor Nr4a1 (Nuclear Receptor Subfamily 4 Group A Member 1) is induced during thymocyte selection and influences regulatory T (Treg) cell development.
  • The specific function of Nr4a1 in CD8(+) T cell development has not been previously defined.

Purpose of the Study:

  • To investigate the role of Nr4a1 in the development and frequency of CD8(+) T cells.
  • To elucidate the molecular mechanisms by which Nr4a1 regulates CD8(+) T cell populations.

Main Methods:

  • Investigated Nr4a1's role in CD8(+) T cell development.
  • Analyzed the transcriptional control of Runx3 by Nr4a1.
  • Examined the recruitment of the corepressor CoREST by Nr4a1.
  • Assessed the impact of Nr4a1 loss on Runx3 expression and CD8(+) T cell numbers.

Main Results:

  • Nr4a1 directly regulates the development and frequency of CD8(+) T cells.
  • Nr4a1 recruits CoREST to suppress Runx3 expression in CD8(+) T cells.
  • Loss of Nr4a1 leads to increased Runx3 expression in thymocytes.
  • Nr4a1 deficiency results in a twofold increase in intrathymic and peripheral CD8(+) T cell numbers.

Conclusions:

  • Nr4a1 is a novel and critical regulator of CD8(+) T cell development.
  • Nr4a1 suppresses CD8(+) T cell expansion through direct transcriptional control of Runx3.

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