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

J Leukoc Biol. 2016 Nov;100(5):1081-1091. doi: 10.1189/jlb.2A0815-368R. Epub 2016 Jun 10.

Abstract

CD4 T cell activation and differentiation mechanisms constitute a complex and intricate signaling network involving several regulatory proteins. IRF2BP2 is a transcriptional repressor that is involved in gene-expression regulation in very diverse biologic contexts. Information regarding the IRF2BP2 regulatory function in CD4 T lymphocytes is very limited and suggests a role for this protein in repressing the expression of different cytokine genes. Here, we showed that Irf2bp2 gene expression was decreased in CD4 T cells upon activation. To investigate the possible regulatory roles for IRF2BP2 in CD4 T cell functions, this protein was ectopically expressed in murine primary-activated CD4 T lymphocytes through retroviral transduction. Interestingly, ectopic expression of IRF2BP2 led to a reduction in CD25 expression and STAT5 phosphorylation, along with an impaired proliferative capacity. The CD69 expression was also diminished in IRF2BP2-overexpressing cells, whereas CD44 and CD62L levels were not altered. In vivo, transferred, IRF2BP2-overexpressing, transduced cells displayed an impaired expansion capacity compared with controls. Furthermore, overexpression of IRF2BP2 in differentiated Th cells resulted in slightly reduced IL-4 and pro-TGF-β production in Th2 and iTregs but had no effect on IFN-γ or IL-17 expression in Th1 and Th17 cells, respectively. Taken together, our data suggest a role for IRF2BP2 in regulating CD4 T cell activation by repressing proliferation and the expression of CD25 and CD69 induced by TCR stimuli.

Keywords: CD25; lymphocyte proliferation; survival.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigens, CD / biosynthesis
  • Antigens, CD / genetics
  • Antigens, Differentiation, T-Lymphocyte / biosynthesis
  • Antigens, Differentiation, T-Lymphocyte / genetics
  • Apoptosis / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • Cytokines / biosynthesis
  • Cytokines / genetics
  • Female
  • Gene Expression Regulation / immunology
  • Humans
  • Interleukin-2 Receptor alpha Subunit / biosynthesis
  • Interleukin-2 Receptor alpha Subunit / genetics
  • Lectins, C-Type / biosynthesis
  • Lectins, C-Type / genetics
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Radiation Chimera
  • Receptors, Antigen, T-Cell / immunology*
  • Recombinant Fusion Proteins / metabolism
  • STAT5 Transcription Factor / metabolism
  • Transcription Factors / immunology*
  • Transduction, Genetic

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD69 antigen
  • Cytokines
  • IRF2BP2 protein, mouse
  • Il2ra protein, mouse
  • Interleukin-2 Receptor alpha Subunit
  • Lectins, C-Type
  • RNA, Messenger
  • Receptors, Antigen, T-Cell
  • Recombinant Fusion Proteins
  • STAT5 Transcription Factor
  • Transcription Factors