IRF2BP2 transcriptional repressor restrains naive CD4 T cell activation and clonal expansion induced by TCR triggering.
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 iTregsbut 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.
Program of Cellular Biology, Brazilian National Cancer Institute, Rio de Janeiro, RJ, Brazil.
Cristiane
C
Sécca
Program of Cellular Biology, Brazilian National Cancer Institute, Rio de Janeiro, RJ, Brazil.
Douglas V
DV
Faget
Program of Cellular Biology, Brazilian National Cancer Institute, Rio de Janeiro, RJ, Brazil.
Steffi C
SC
Hanschke
Program of Molecular Carcinogenesis, Brazilian National Cancer Institute, Rio de Janeiro, RJ, Brazil.
Mayra S
MS
Carneiro
Program of Molecular Carcinogenesis, Brazilian National Cancer Institute, Rio de Janeiro, RJ, Brazil.|Reference Laboratories, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil; and.
Martin H
MH
Bonamino
Program of Cellular Biology, Brazilian National Cancer Institute, Rio de Janeiro, RJ, Brazil.|Department of Immunobiology, Fluminense Federal University, Rio de Janeiro, RJ, Brazil.
Patricia S
PS
de-Araujo-Souza
Program of Cellular Biology, Brazilian National Cancer Institute, Rio de Janeiro, RJ, Brazil; jpviola@inca.gov.br.
João P B
JP
Viola
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000235:genetics; D017209:Apoptosis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis / Q000235:genetics; D037181:Lectins, C-Type / Q000096:biosynthesis / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011828:Radiation Chimera; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism; D014157:Transcription Factors / Q000276:immunology*; D014161:Transduction, Genetic; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D016207:Cytokines; D053645:Interleukin-2 Receptor alpha Subunit; D037181:Lectins, C-Type; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; D050799:STAT5 Transcription Factor; D014157:Transcription Factors; D000099192:CD69 Antigens; C000603862:IRF2BP2 protein, mouse; C508018:Il2ra protein, mouse
CD25; lymphocyte proliferation; survival