Regulation of GATA-3 expression during CD4 lineage differentiation1

نویسندگان

  • Idoia Gimferrer
  • Taishan Hu
  • Amie Simmons
  • Chi Wang
  • Abdallah Souabni
  • Meinrad Busslinger
  • Timothy P. Bender
  • Gabriela Hernandez-Hoyos
  • José Alberola-Ila
چکیده

GATA-3 is necessary for the development of MHC II-restricted CD4 T cells, and its expression is increased during positive selection of these cells. TcR signals drive this upregulation, but the signaling pathways that control this process are not well understood. Using genetic and pharmacological approaches we show that GATA-3 upregulation during thymocyte positive selection is the result of additive inputs from the Ras/MAPK and Calcineurin pathways. This upregulation requires the presence of the transcription factor c-Myb. Furthermore, we show that TH-POK can also upregulate GATA-3 in double positive thymocytes, suggesting the existence of a positive feedback loop that contributes to lock in the initial commitment to the CD4 lineage during differentiation.

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تاریخ انتشار 2011