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The transcription factor BATF operates as an essential differentiation checkpoint in early effector CD8+ T cells.

Abstract：

:The transcription factor BATF is required for the differentiation of interleukin 17 (IL-17)-producing helper T cells (TH17 cells) and follicular helper T cells (TFH cells). Here we identified a fundamental role for BATF in regulating the differentiation of effector of CD8(+) T cells. BATF-deficient CD8(+) T cells showed profound defects in effector population expansion and underwent proliferative and metabolic catastrophe early after encountering antigen. BATF, together with the transcription factors IRF4 and Jun proteins, bound to and promoted early expression of genes encoding lineage-specific transcription-factors (T-bet and Blimp-1) and cytokine receptors while paradoxically repressing genes encoding effector molecules (IFN-γ and granzyme B). Thus, BATF amplifies T cell antigen receptor (TCR)-dependent expression of transcription factors and augments the propagation of inflammatory signals but restrains the expression of genes encoding effector molecules. This checkpoint prevents irreversible commitment to an effector fate until a critical threshold of downstream transcriptional activity has been achieved.

journal_name

Nat Immunol

journal_title

Nature immunology

authors

Kurachi M,Barnitz RA,Yosef N,Odorizzi PM,DiIorio MA,Lemieux ME,Yates K,Godec J,Klatt MG,Regev A,Wherry EJ,Haining WN

doi

10.1038/ni.2834

subject

Has Abstract

pub_date

2014-04-01 00:00:00

pages

373-83

issue

4

eissn

1529-2908

issn

1529-2916

pii

ni.2834

journal_volume

15

pub_type

杂志文章

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