1. Computational and Systems Biology
  2. Immunology and Inflammation

Longitudinal analysis of invariant natural killer T cell activation reveals a cMAF-associated transcriptional state of NKT10 cells

  1. Harry Kane
  2. Nelson M LaMarche
  3. Áine Ní Scannail
  4. Amanda E Garza
  5. Hui-Fern Koay
  6. Adiba I Azad
  7. Britta Kunkenmoeller
  8. Brenneth Stevens
  9. Michael P Brenner
  10. Lydia Lynch  Is a corresponding author
  1. Trinity College Dublin, Ireland
  2. Brigham and Women's Hospital, United States
  3. University of Melbourne, Australia
https://doi.org/10.7554/eLife.76586
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  1. Harry Kane
  2. Nelson M LaMarche
  3. Áine Ní Scannail
  4. Amanda E Garza
  5. Hui-Fern Koay
  6. Adiba I Azad
  7. Britta Kunkenmoeller
  8. Brenneth Stevens
  9. Michael P Brenner
  10. Lydia Lynch
(2022)
Longitudinal analysis of invariant natural killer T cell activation reveals a cMAF-associated transcriptional state of NKT10 cells
eLife 11:e76586.
https://doi.org/10.7554/eLife.76586
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  3. Download .RIS

Abstract

Innate T cells, including CD1d-restricted invariant natural killer T (iNKT) cells, are characterized by their rapid activation in response to non-peptide antigens, such as lipids. While the transcriptional profiles of naive, effector and memory adaptive T cells have been well studied, less is known about transcriptional regulation of different iNKT cell activation states. Here, using single cell RNA-sequencing, we performed longitudinal profiling of activated murine iNKT cells, generating a transcriptomic atlas of iNKT cell activation states. We found that transcriptional signatures of activation are highly conserved among heterogeneous iNKT cell populations, including NKT1, NKT2 and NKT17 subsets, and human iNKT cells. Strikingly, we found that regulatory iNKT cells, such as adipose iNKT cells, undergo blunted activation, and display constitutive enrichment of memory-like cMAF+ and KLRG1+ populations. Moreover, we identify a conserved cMAF-associated transcriptional network among NKT10 cells, providing novel insights into the biology of regulatory and antigen experienced iNKT cells.

Data availability

Sequencing data have been deposited in GEO under accession code GSE190201.

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

Article and author information

Author details

  1. Harry Kane

    Trinity Biomedical Science Institute, Trinity College Dublin, Dublin, Ireland
    Competing interests
    The authors declare that no competing interests exist.

  2. Nelson M LaMarche

    Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Áine Ní Scannail

    Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Amanda E Garza

    Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Hui-Fern Koay

    Department of Microbiology and Immunology, University of Melbourne, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.

  6. Adiba I Azad

    Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Britta Kunkenmoeller

    Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.

  8. Brenneth Stevens

    Trinity Biomedical Science Institute, Trinity College Dublin, Dublin, Ireland
    Competing interests
    The authors declare that no competing interests exist.

  9. Michael P Brenner

    Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.

  10. Lydia Lynch

    Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Boston, United States
    For correspondence
    llynch@bwh.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4273-4681

Funding

American Diabetes Association (1-16-JDF-061)

  • Lydia Lynch

National Institutes of Health (R01AI134861)

  • Lydia Lynch

European Research Council (679173)

  • Lydia Lynch

Science Foundation Ireland

  • Harry Kane
  • Lydia Lynch

National Institutes of Health (AI113046)

  • Michael P Brenner

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All animal work was approved and conducted in compliance with the Trinity College Dublin University Ethics Committee and the Health Products Regulatory Authority Ireland, and the Institutional Animal Care and Use Committee guidelines of The Dana Farber Cancer Institute and Harvard Medical School.

Copyright

© 2022, Kane 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. Harry Kane
  2. Nelson M LaMarche
  3. Áine Ní Scannail
  4. Amanda E Garza
  5. Hui-Fern Koay
  6. Adiba I Azad
  7. Britta Kunkenmoeller
  8. Brenneth Stevens
  9. Michael P Brenner
  10. Lydia Lynch
(2022)
Longitudinal analysis of invariant natural killer T cell activation reveals a cMAF-associated transcriptional state of NKT10 cells
eLife 11:e76586.
https://doi.org/10.7554/eLife.76586

Share this article

https://doi.org/10.7554/eLife.76586

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