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

Nat Immunol
Authors
Keywords
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.

Year of Publication
2014
Journal
Nat Immunol
Volume
15
Issue
4
Pages
373-83
Date Published
2014 Apr
ISSN
1529-2916
URL
DOI
10.1038/ni.2834
PubMed ID
24584090
PubMed Central ID
PMC4000237
Links
Grant list
U19 AI083022 / AI / NIAID NIH HHS / United States
AI083022 / AI / NIAID NIH HHS / United States
AI082630 / AI / NIAID NIH HHS / United States
R01 AI091493 / AI / NIAID NIH HHS / United States
U19 AI082630 / AI / NIAID NIH HHS / United States
T32 AI00762 / AI / NIAID NIH HHS / United States
AI095608 / AI / NIAID NIH HHS / United States
HHSN266200500030C / PHS HHS / United States
U01 AI095608 / AI / NIAID NIH HHS / United States
AI091493 / AI / NIAID NIH HHS / United States
HHSN266200500030C / AI / NIAID NIH HHS / United States