The transcription factor Bach2 negatively regulates murine natural killer cell maturation and function
- Washington University in St. Louis, United States
- Osaka University, Japan
Abstract
BTB domain And CNC Homolog 2 (Bach2) is a transcription repressor that actively participates in T and B lymphocyte development, but it is unknown if Bach2 is also involved in the development of innate immune cells, such as natural killer (NK) cells. Here, we followed the expression of Bach2 during murine NK cell development, finding that it peaked in immature CD27+CD11b+ cells and decreased upon further maturation. Bach2 showed an organ and tissue-specific expression pattern in NK cells. Bach2 expression positively correlated with the expression of transcription factor TCF1 and negatively correlated with genes encoding NK effector molecules and those involved in the cell cycle. Lack of Bach2 expression caused changes in chromatin accessibility of corresponding genes. In the end, Bach2-deficiency resulted in increased proportions of terminally differentiated NK cells with increased production of granzymes and cytokines. NK cell-mediated control of tumor metastasis was also augmented in the absence of Bach2. Therefore, Bach2 is a key checkpoint protein regulating NK terminal maturation.
Data availability
RNA-sequencing data have been deposited in NCBI's Gene Expression Omnibus and are accessible through GEO Series accession number GSE196530.ATAC-seq data have been deposited in NCBI's Gene Expression Omnibus and are accessible through GEO Series accession number GSE212807.Previously published datasets are available on NCBI's Gene Expression Omnibus under the accession number GSE83978 and GSE77857.
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Bach2 negatively regulates natural killer cell maturation and effector programNCBI Gene Expression Omnibus, GSE196530.
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Chromatin accessibility of transcription factor Bach2 in mouse NK cells (ATAC-seq)NCBI Gene Expression Omnibus, GSE212807.
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Memory-like CD8 T-cells sustain the immune response to chronic viral infectionsNCBI Gene Expression Omnibus, GSE83978.
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BACH2 regulates CD8+ T cell differentiation by controlling access of AP-1 factors to enhancersNCBI Gene Expression Omnibus, GSE77857.
Article and author information
Author details
Funding
National Institute of Allergy and Infectious Diseases (R01-AI129545)
- Wayne M Yokoyama
National Human Genome Research Institute (R01-HG007175)
- Ting Wang
National Human Genome Research Institute (U01-HG009391)
- Ting Wang
National Human Genome Research Institute (U41-HG010972)
- Ting Wang
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Gabrielle T Belz, The University of Queensland, Australia
Ethics
Animal experimentation: Mouse studies were conducted in accordance with the institutional ethical guidelines through institutional animal care and use committee (IACUC) protocol that was approved by the Animal Studies Committee of Washington University (#20180293).
Version history
- Received: January 24, 2022
- Preprint posted: February 14, 2022 (view preprint)
- Accepted: October 2, 2022
- Accepted Manuscript published: October 3, 2022 (version 1)
- Version of Record published: October 13, 2022 (version 2)
Copyright
© 2022, Li et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The transcription factor Bach2 negatively regulates murine natural killer cell maturation and function
eLife 11:e77294.
https://doi.org/10.7554/eLife.77294
Further reading
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