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

ABSTRACT: 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-?B. In Tconv cells, NF-?B regulates expression of genes essential for T cell activation, proliferation, and function. However the role of NF-?B in Treg function remains unclear. We conditionally deleted canonical NF-?B 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-?B p65 binding analyses demonstrated a lineage specific, NF-?B-dependent transcriptional program, enabled by enhanced chromatin accessibility. These dual roles of canonical NF-?B in Tconv and Treg cells highlight the functional plasticity of the NF-?B signaling pathway and underscores the need for more selective strategies to therapeutically target NF-?B.

SUBMITTER: Oh H 

PROVIDER: S-EPMC5679261 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature