3 years ago

An NF-κB Transcription-Factor-Dependent Lineage-Specific Transcriptional Program Promotes Regulatory T Cell Identity and Function

An NF-κB Transcription-Factor-Dependent Lineage-Specific Transcriptional Program Promotes Regulatory T Cell Identity and Function
Sankar Ghosh, Yenkel Grinberg-Bleyer, Dillon Maloney, Dev M. Bhatt, Raul Rabadan, Matthew S. Hayden, Will Liao, Hyunju Oh, Zikai Wu, Pingzhang Wang, Ulf Klein, Roland M. Schmid, Nicole Heise, Jiguang Wang

Summary

Both conventional T (Tconv) cells and regulatory T (Treg) cells are activated through ligation of the T cell receptor (TCR) complex, leading to the induction of the transcription factor NF-κB. In Tconv cells, NF-κB regulates expression of genes essential for T cell activation, proliferation, and function. However the role of NF-κB in Treg function remains unclear. We conditionally deleted canonical NF-κB members p65 and c-Rel in developing and mature Treg cells and found they have unique but partially redundant roles. c-Rel was critical for thymic Treg development while p65 was essential for mature Treg identity and maintenance of immune tolerance. Transcriptome and NF-κB p65 binding analyses demonstrated a lineage specific, NF-κB-dependent transcriptional program, enabled by enhanced chromatin accessibility. These dual roles of canonical NF-κB in Tconv and Treg cells highlight the functional plasticity of the NF-κB signaling pathway and underscores the need for more selective strategies to therapeutically target NF-κB.

Publisher URL: http://www.cell.com/immunity/fulltext/S1074-7613(17)30368-0

DOI: 10.1016/j.immuni.2017.08.010

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