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IRF2BP2 transcriptional repressor restrains naive CD4 T cell activation and clonal expansion induced by TCR

Cristiane Sécca1, Douglas V Faget1, Steffi C Hanschke1

  • 1Program of Cellular Biology, Brazilian National Cancer Institute, Rio de Janeiro, RJ, Brazil.

Journal of Leukocyte Biology
|June 12, 2016
PubMed

Insights

IRF2BP2, a transcriptional repressor, limits CD4 T cell activation by inhibiting proliferation and reducing CD25 and CD69 expression upon T cell receptor stimulation.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • CD4 T cell activation involves complex signaling networks with poorly understood regulatory proteins.
  • IRF2BP2 is a known transcriptional repressor with limited information on its role in CD4 T lymphocytes.
  • Existing data suggest IRF2BP2 may repress cytokine gene expression in CD4 T cells.

Purpose of the Study:

  • To investigate the regulatory function of IRF2BP2 in CD4 T cell activation and differentiation.
  • To determine the impact of IRF2BP2 overexpression on key T cell activation markers and functions.

Main Methods:

  • Ectopic expression of IRF2BP2 in murine primary activated CD4 T lymphocytes via retroviral transduction.
  • Analysis of CD25, CD69, CD44, CD62L expression, and STAT5 phosphorylation.
  • Assessment of cell proliferation and in vivo expansion capacity.
  • Evaluation of cytokine production (IL-4, TGF-β, IFN-γ, IL-17) in differentiated T helper subsets.

Main Results:

  • Irf2bp2 gene expression decreased upon CD4 T cell activation.
  • Ectopic IRF2BP2 expression reduced CD25 and CD69 levels and impaired T cell proliferation.
  • IRF2BP2 overexpression diminished STAT5 phosphorylation and in vivo cell expansion.
  • Reduced IL-4 and pro-TGF-β production in Th2 and iTregs, with no effect on Th1/Th17 cytokines.

Conclusions:

  • IRF2BP2 acts as a negative regulator of CD4 T cell activation.
  • IRF2BP2 represses T cell receptor-induced proliferation, CD25, and CD69 expression.
  • IRF2BP2 influences cytokine production in specific T helper cell subsets.
Keywords:
CD25lymphocyte proliferationsurvival

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