The transcription factor Bach2 negatively regulates murine natural killer cell maturation and function

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.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Shasha Li

    Department of Medicine, Washington University in St. Louis, St Louis, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5924-6396
  2. Michael D Bern

    Department of Medicine, Washington University in St. Louis, St Louis, United States
    Competing interests
    No competing interests declared.
  3. Benpeng Miao

    Department of Genetics, Washington University in St. Louis, St Louis, United States
    Competing interests
    No competing interests declared.
  4. Changxu Fan

    Department of Genetics, Washington University in St. Louis, St Louis, United States
    Competing interests
    No competing interests declared.
  5. Xiaoyun Xing

    Department of Genetics, Washington University in St. Louis, St Louis, United States
    Competing interests
    No competing interests declared.
  6. Takeshi Inoue

    Laboratory of Lymphocyte Differentiation, Osaka University, Osaka, Japan
    Competing interests
    No competing interests declared.
  7. Sytse J Piersma

    Department of Medicine, Washington University in St. Louis, St Louis, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5379-3556
  8. Ting Wang

    Department of Genetics, Washington University in St. Louis, St Louis, United States
    Competing interests
    No competing interests declared.
  9. Marco Colonna

    Department of Pathology and Immunology, Washington University in St. Louis, St Louis, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5222-4987
  10. Tomohiro Kurosaki

    Laboratory of Lymphocyte Differentiation, Osaka University, Osaka, Japan
    Competing interests
    Tomohiro Kurosaki, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6352-304X
  11. Wayne M Yokoyama

    Department of Medicine, Washington University in St. Louis, St Louis, United States
    For correspondence
    yokoyama@wustl.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0566-7264

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

  1. 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

  1. Received: January 24, 2022
  2. Preprint posted: February 14, 2022 (view preprint)
  3. Accepted: October 2, 2022
  4. Accepted Manuscript published: October 3, 2022 (version 1)
  5. 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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  1. Shasha Li
  2. Michael D Bern
  3. Benpeng Miao
  4. Changxu Fan
  5. Xiaoyun Xing
  6. Takeshi Inoue
  7. Sytse J Piersma
  8. Ting Wang
  9. Marco Colonna
  10. Tomohiro Kurosaki
  11. Wayne M Yokoyama
(2022)
The transcription factor Bach2 negatively regulates murine natural killer cell maturation and function
eLife 11:e77294.
https://doi.org/10.7554/eLife.77294

Share this article

https://doi.org/10.7554/eLife.77294

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    Prinflammatory extracellular chromatin from neutrophil extracellular traps (NETs) and other cellular sources is found in COVID-19 patients and may promote pathology. We determined whether pulmonary administration of the endonuclease dornase alfa reduced systemic inflammation by clearing extracellular chromatin.

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    Funding:

    LifeArc, Breathing Matters, The Francis Crick Institute (CRUK, Medical Research Council, Wellcome Trust).

    Clinical trial number:

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