TY - JOUR
T1 - The E-Id Protein Axis Specifies Adaptive Lymphoid Cell Identity and Suppresses Thymic Innate Lymphoid Cell Development
AU - Miyazaki, Masaki
AU - Miyazaki, Kazuko
AU - Chen, Kenian
AU - Jin, Yi
AU - Turner, Jacob
AU - Moore, Amanda J.
AU - Saito, Rintaro
AU - Yoshida, Kenichi
AU - Ogawa, Seishi
AU - Rodewald, Hans Reimer
AU - Lin, Yin C.
AU - Kawamoto, Hiroshi
AU - Murre, Cornelis
N1 - Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/5/16
Y1 - 2017/5/16
N2 - 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.
AB - 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.
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U2 - 10.1016/j.immuni.2017.04.022
DO - 10.1016/j.immuni.2017.04.022
M3 - Article
C2 - 28514688
AN - SCOPUS:85019479989
SN - 1074-7613
VL - 46
SP - 818-834.e4
JO - Immunity
JF - Immunity
IS - 5
ER -
