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Immunity. 2017 May 16;46(5):818-834.e4. doi: 10.1016/j.immuni.2017.04.022.

The E-Id Protein Axis Specifies Adaptive Lymphoid Cell Identity and Suppresses Thymic Innate Lymphoid Cell Development.

Author information

1
Department of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan; Department of Molecular Biology, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: mmiyazaki@infront.kyoto-u.ac.jp.
2
Department of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan; Department of Molecular Biology, University of California, San Diego, La Jolla, CA 92093, USA.
3
Baylor Research Institute, Baylor Institute for Immunology Research, Dallas, TX 75246, USA.
4
Department of Molecular Biology, University of California, San Diego, La Jolla, CA 92093, USA.
5
Institute of Metabolomic Medicine and Center for Renal Translational Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
6
Department of Pathology and Tumor Biology, Kyoto University, Kyoto 606-8507, Japan.
7
Division of Cellular Immunology, German Cancer Research Center, Im Neuenheimer Field 280, 69120 Heidelberg, Germany.
8
Department of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
9
Department of Molecular Biology, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: murre@biomail.ucsd.edu.

Abstract

Innate and adaptive lymphoid development is orchestrated by the activities of E proteins and their antagonist Id proteins, but how these factors regulate early T cell progenitor (ETP) and innate lymphoid cell (ILC) development remains unclear. Using multiple genetic strategies, we demonstrated that E proteins E2A and HEB acted in synergy in the thymus to establish T cell identity and to suppress the aberrant development of ILCs, including ILC2s and lymphoid-tissue-inducer-like cells. E2A and HEB orchestrated T cell fate and suppressed the ILC transcription signature by activating the expression of genes associated with Notch receptors, T cell receptor (TCR) assembly, and TCR-mediated signaling. E2A and HEB acted in ETPs to establish and maintain a T-cell-lineage-specific enhancer repertoire, including regulatory elements associated with the Notch1, Rag1, and Rag2 loci. On the basis of these and previous observations, we propose that the E-Id protein axis specifies innate and adaptive lymphoid cell fate.

KEYWORDS:

E-ID protein axis; E2A; HEB; Notch signaling; T cell development; basic helix-loop-helix transcription factor; early T cell progenitor; innate lymphoid cell; regulome

PMID:
28514688
PMCID:
PMC5512722
DOI:
10.1016/j.immuni.2017.04.022
[Indexed for MEDLINE]
Free PMC Article

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