Abstract

Multiple sclerosis (MS) is a chronic demyelinating disease characterised by immune cell infiltration resulting in lesions that preferentially affect periventricular areas of the brain. Despite research efforts to define the role of various immune cells in MS pathogenesis, the focus has been on a few immune cell populations while full-spectrum analysis, encompassing others such as natural killer (NK) cells, has not been performed. Here, we used single-cell mass cytometry (CyTOF) to profile the immune landscape of brain periventricular areas - septum and choroid plexus – and of the circulation from donors with MS, dementia and controls without neurological disease. Using a 37-marker panel, we revealed the infiltration of T cells and antibody-secreting cells in periventricular brain regions and identified a novel NK cell signature specific to MS. CD56bright NK cells were accumulated in the septum of MS donors and displayed an activated and migratory phenotype, similar to that of CD56bright NK cells in the circulation. We validated this signature by multiplex immunohistochemistry and found that the number of NK cells with high expression of granzyme K, typical of the CD56bright subset, was increased in both periventricular lesions and the choroid plexus of donors with MS. Together, our multi-tissue single-cell data shows that CD56bright NK cells accumulate in the periventricular brain regions of MS patients, bringing NK cells back to the spotlight of MS pathology.

Data availability

FCS CyTOF files are uploaded to http://flowrepository.org with IDs FR-FCM-Z4JJ (raw) and FR=FCM-Z4JK (normalised).Code used in this analysis is available on the github repository https://github.com/orgs/MolecularCellBiologyImmunology/cytof-periventricular-ms

The following data sets were generated

Article and author information

Author details

  1. Sabela Rodríguez-Lorenzo

    Department of Molecular Cell Biology and Immunology, Amsterdam UMC Location VUmc, Amsterdam, Netherlands
    For correspondence
    s.rodriguezlorenzo@amsterdamumc.nl
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5956-4519
  2. Lynn van Olst

    Department of Molecular Cell Biology and Immunology, Amsterdam UMC Location VUmc, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7569-0470
  3. Carla Rodriguez-Mogeda

    Department of Molecular Cell Biology and Immunology, Amsterdam UMC Location VUmc, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  4. Alwin Kamermans

    Department of Molecular Cell Biology and Immunology, Amsterdam UMC Location VUmc, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3601-395X
  5. Susanne MA van der Pol

    Department of Molecular Cell Biology and Immunology, Amsterdam UMC Location VUmc, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  6. Ernesto Rodríguez

    Department of Molecular Cell Biology and Immunology, Amsterdam UMC Location VUmc, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  7. Gijs Kooij

    Department of Molecular Cell Biology and Immunology, Amsterdam UMC Location VUmc, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9488-2918
  8. Helga E de Vries

    Department of Molecular Cell Biology and Immunology, Amsterdam UMC Location VUmc, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.

Funding

Stichting MS Research (20-1087)

  • Ernesto Rodríguez
  • Gijs Kooij
  • Helga E de Vries

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

Reviewing Editor

  1. Beth Stevens, Boston Children's Hospital, United States

Ethics

Human subjects: Post-mortem tissue was obtained from donors by rapid autopsy from the Netherlands Brain Bank and Multiple Sclerosis Society Tissue Bank. All donors or their next of kin provided fully informed consent for autopsy and use of material for research from Netherlands Brain Bank under ethical approval by the Medical Ethics Committee of the Free University Medical Center in Amsterdam (2009/148), project number 1127.

Version history

  1. Received: September 13, 2021
  2. Preprint posted: September 20, 2021 (view preprint)
  3. Accepted: April 29, 2022
  4. Accepted Manuscript published: May 10, 2022 (version 1)
  5. Version of Record published: May 26, 2022 (version 2)

Copyright

© 2022, Rodríguez-Lorenzo 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. Sabela Rodríguez-Lorenzo
  2. Lynn van Olst
  3. Carla Rodriguez-Mogeda
  4. Alwin Kamermans
  5. Susanne MA van der Pol
  6. Ernesto Rodríguez
  7. Gijs Kooij
  8. Helga E de Vries
(2022)
Single-cell profiling reveals periventricular CD56bright NK cell accumulation in multiple sclerosis
eLife 11:e73849.
https://doi.org/10.7554/eLife.73849

Share this article

https://doi.org/10.7554/eLife.73849

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