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E protein transcription factors are required for the development of CD4(+) lineage T cells.

Immunity | Mar 23, 2012

http://www.ncbi.nlm.nih.gov/pubmed/22425249

The double-positive (DP) to single-positive (SP) transition during T cell development is initiated by downregulation of the E protein transcription factors HEB and E2A. Here, we have demonstrated that in addition to regulating the onset of this transition, HEB and E2A also play a separate role in CD4(+) lineage choice. Deletion of HEB and E2A in DP thymocytes specifically blocked the development of CD4(+) lineage T cells. Furthermore, deletion of the E protein inhibitors Id2 and Id3 allowed CD4(+) T cell development but blocked CD8(+) lineage development. Analysis of the CD4(+) lineage transcriptional regulators ThPOK and Gata3 placed HEB and E2A upstream of CD4(+) lineage specification. These studies identify an important role for E proteins in the activation of CD4(+) lineage differentiation as thymocytes undergo the DP to SP transition.

Pubmed ID: 22425249 RIS Download

Mesh terms: Animals | Antigens, CD4 | Basic Helix-Loop-Helix Transcription Factors | CD4-Positive T-Lymphocytes | CD8-Positive T-Lymphocytes | Cell Differentiation | Inhibitor of Differentiation Protein 2 | Inhibitor of Differentiation Proteins | Interleukin-7 Receptor alpha Subunit | Mice | Mice, 129 Strain | Mice, Inbred C57BL | Mice, Knockout | Mice, Transgenic | Receptors, CCR7 | Up-Regulation

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Associated grants

  • Agency: NCI NIH HHS, Id: R01 CA153260
  • Agency: NIGMS NIH HHS, Id: R01 GM059638
  • Agency: NIGMS NIH HHS, Id: R01 GM059638-09A1
  • Agency: NIGMS NIH HHS, Id: R01 GM059638-10
  • Agency: NIGMS NIH HHS, Id: R01 GM059638-11
  • Agency: NIGMS NIH HHS, Id: R01 GM059638-12
  • Agency: NIGMS NIH HHS, Id: R01GM059638

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