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

ABSTRACT: 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.

SUBMITTER: Jones-Mason ME

PROVIDER: S-EPMC3431168 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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

Jones-Mason Mary Elizabeth ME Zhao Xudong X Kappes Dietmar D Lasorella Anna A Iavarone Antonio A Zhuang Yuan Y

Immunity 20120315 3

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( ...[more]

PMID: 22425249

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