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Nat Immunol. 2016 Jul;17(7):851-860. doi: 10.1038/ni.3441. Epub 2016 May 9.

BACH2 regulates CD8(+) T cell differentiation by controlling access of AP-1 factors to enhancers.

Author information

1
National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD., USA.
2
Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, UK.
3
Medical Scientist Training Program, Ohio State University College of Medicine, Columbus, OH., USA.
4
Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung and Blood Institute (NHLBI), NIH, Bethesda, MD., USA.
5
Systems Biology Center, NHLBI, NIH, Bethesda, MD., USA.
6
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD., USA.
7
Institute for Infection & Immunity, St. George's University of London, London, UK.
8
Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD., USA.
9
Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.
10
AMED-CREST, Japan Agency for Medical Research and Development, Tokyo, Japan.
#
Contributed equally

Abstract

T cell antigen receptor (TCR) signaling drives distinct responses depending on the differentiation state and context of CD8(+) T cells. We hypothesized that access of signal-dependent transcription factors (TFs) to enhancers is dynamically regulated to shape transcriptional responses to TCR signaling. We found that the TF BACH2 restrains terminal differentiation to enable generation of long-lived memory cells and protective immunity after viral infection. BACH2 was recruited to enhancers, where it limited expression of TCR-driven genes by attenuating the availability of activator protein-1 (AP-1) sites to Jun family signal-dependent TFs. In naive cells, this prevented TCR-driven induction of genes associated with terminal differentiation. Upon effector differentiation, reduced expression of BACH2 and its phosphorylation enabled unrestrained induction of TCR-driven effector programs.

PMID:
27158840
PMCID:
PMC4918801
DOI:
10.1038/ni.3441
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

The authors declare no competing financial interests.

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