RESUMO
Recently, it was reported that the expression of Runt-related transcription factor 3 (Runx3) is up-regulated in CD4(+) helper T cells during Th1 cell differentiation, and that Runx3 functions in a positive feed-forward manner with the T-box family transcription factor, T-bet, which is a master regulator of Th1 cell differentiation. The relative expression levels of IFN-gamma and IL-4 are also regulated by the Th2-associated transcription factor, GATA3. Here, we demonstrate that Runx3 was induced in Th2 as well as Th1 cells and that Runx3 interacted with GATA3 and attenuated GATA3 transcriptional activity. Ectopic expression of Runx3 in vitro in cultured cells or transgenic expression of Runx3 in mice accelerated CD4(+) cells to a Th1-biased population or down-modulated Th2 responses, in part by neutralizing GATA3. Our results suggest that the balance of Runx3 and GATA3 is one factor that influences the manifestation of CD4(+) cells as the Th1 or Th2 phenotypes.
Assuntos
Comunicação Celular/imunologia , Subunidade alfa 3 de Fator de Ligação ao Core/fisiologia , Regulação para Baixo/imunologia , Fator de Transcrição GATA3/metabolismo , Imunofenotipagem , Células Th1/imunologia , Células Th2/imunologia , Células Th2/metabolismo , Adjuvantes Imunológicos/metabolismo , Adjuvantes Imunológicos/fisiologia , Animais , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Linhagem Celular , Células Cultivadas , Subunidade alfa 3 de Fator de Ligação ao Core/metabolismo , Fator de Transcrição GATA3/antagonistas & inibidores , Fator de Transcrição GATA3/biossíntese , Fator de Transcrição GATA3/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Células Th1/citologia , Células Th1/metabolismo , Células Th2/citologiaRESUMO
In the evolution of primates, the common marmoset belongs to the new world monkey family and is distinct from the great ape family (which includes humans). In this study, we predicted the amino acid sequences of 30 immunity-related genes from the common marmoset and compared them with those from human and mouse. The domain composition of each orthologous protein was analyzed by the SMART tool and was found to be the same among the three species. A BLAST search revealed that the common marmoset and human proteins were 86% identical on average, whereas the conservation between the common marmoset and mouse or between the human and mouse was only 60%. This indicates that the common marmoset and human proteins are closely related and are similarly divergent from the mouse. We divided the 30 proteins into two categories based on the degree of conservation between the common marmoset and mouse amino acid sequences. One group included 19 proteins and had a relatively high level of conservation (68% identical), whereas the other 11 proteins were less conserved (45% identical). This suggests that these immunity-related genes do not evolve at a uniform rate. Interestingly, however, ligand/receptor pairs such as interleukin-6 and interleukin-6 receptor appear to have evolved simultaneously.