The E-Id Protein Axis Specifies Innate and Adaptive Lymphoid Cell Fate

• Published in: Immunity (Cambridge, Mass.) Vol. 46; no. 5; pp. 818 - 834.e4
• Main Authors: Miyazaki, Masaki, Miyazaki, Kazuko, Chen, Kenian, Jin, Yi, Turner, Jacob, Moore, Amanda J., Saito, Rintaro, Yoshida, Kenichi, Ogawa, Seishi, Rodewald, Hans-Reimer, Lin, Yin C., Kawamoto, Hiroshi, Murre, Cornelis
• Format: Journal Article
• Language: English
• Published: 16.05.2017
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2017.04.022

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 and Rag1/2 gene loci. Based on these and previous observations we propose that the E-Id protein axis specifies innate versus adaptive lymphoid cell fate.