BACH2 enforces the transcriptional and epigenetic programs of stem-like CD8+ T cells

Yao C, Lou G, Sun HW, Zhu Z, Sun Y, Chen Z, Chauss D, Moseman EA, Cheng J, D'Antonio MA, Shi W, Shi J, Kometani K, Kurosaki T, Wherry EJ, Afzali B, Gattinoni L, Zhu Y, Mcgavern DB, O'Shea JJ, Schwartzberg PL, Wu T (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Nature Immunology Nature Research

Book Volume: 22

Pages Range: 370-380

Journal Issue: 3

DOI: 10.1038/s41590-021-00868-7

Abstract

During chronic infection and cancer, a self-renewing CD8+ T cell subset maintains long-term immunity and is critical to the effectiveness of immunotherapy. These stem-like CD8+ T cells diverge from other CD8+ subsets early after chronic viral infection. However, pathways guarding stem-like CD8+ T cells against terminal exhaustion remain unclear. Here, we show that the gene encoding transcriptional repressor BACH2 is transcriptionally and epigenetically active in stem-like CD8+ T cells but not terminally exhausted cells early after infection. BACH2 overexpression enforced stem-like cell fate, whereas BACH2 deficiency impaired stem-like CD8+ T cell differentiation. Single-cell transcriptomic and epigenomic approaches revealed that BACH2 established the transcriptional and epigenetic programs of stem-like CD8+ T cells. In addition, BACH2 suppressed the molecular program driving terminal exhaustion through transcriptional repression and epigenetic silencing. Thus, our study reveals a new pathway that enforces commitment to stem-like CD8+ lineage and prevents an alternative terminally exhausted cell fate.

Involved external institutions

University of Colorado System US United States (USA) (US) Duke University US United States (USA) (US) National Human Genome Research Institute (NHGRI) US United States (USA) (US) University of Pennsylvania US United States (USA) (US) Riken Institute of Physical and Chemical Research / 理化学研究所 JP Japan (JP) National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK / NIDDKD) US United States (USA) (US) US National Institutes of Health (NIH) US United States (USA) (US) Universität Regensburg DE Germany (DE) National Institute of Neurological Disorders and Stroke (NINDS) US United States (USA) (US)

How to cite

APA:

Yao, C., Lou, G., Sun, H.-W., Zhu, Z., Sun, Y., Chen, Z.,... Wu, T. (2021). BACH2 enforces the transcriptional and epigenetic programs of stem-like CD8+ T cells. Nature Immunology, 22(3), 370-380. https://doi.org/10.1038/s41590-021-00868-7

MLA:

Yao, Chen, et al. "BACH2 enforces the transcriptional and epigenetic programs of stem-like CD8+ T cells." Nature Immunology 22.3 (2021): 370-380.

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