Multiplexed imaging of immune cells in staged multiple sclerosis lesions by mass cytometry
- University of Toronto, Canada
- Yale School of Medicine, United States
- Université de Montreal, Canada
- University Health Network, Canada
- Fluidigm Inc, Canada
- Université de Montréal, Canada
Abstract
Multiple Sclerosis (MS) is characterized by demyelinated and inflammatory lesions in the brain and spinal cord that are highly variable in terms of cellular content. Here we used imaging mass cytometry (IMC) to enable the simultaneous imaging of 15+ proteins within staged MS lesions. To test the potential for IMC to discriminate between different types of lesions, we selected a case with severe rebound MS disease activity after natalizumab cessation. With post-acquisition analysis pipelines we were able to: (1) Discriminate demyelinating macrophages from the resident microglial pool; (2) Determine which types of lymphocytes reside closest to blood vessels; (3) Identify multiple subsets of T and B cells, and (4) Ascertain dynamics of T cell phenotypes vis-à-vis lesion type and location. We propose that IMC will enable a comprehensive analysis of single-cell phenotypes, their functional states and cell-cell interactions in relation to lesion morphometry and demyelinating activity in MS patients.
Data availability
All data generated and analysed during this study are included in the manuscript and supporting files. Source data file has been provided for Figure 7.
Article and author information
Author details
Funding
National Multiple Sclerosis Society (RR-1602-07777)
- Valeria Ramaglia
Multiple Sclerosis Society of Canada
- Jennifer L Gommerman
Multiple Sclerosis Society of Canada
- Alexandre Prat
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Isaac M Chiu, Harvard Medical School, United States
Ethics
Human subjects: This work included the use of post-mortem brain tissue. Written consent for post-mortem donation of the CNS to research from the MS donor was obtained (ethics committee approval number BH.07.001).Ethical approval for the use of post-mortem brain tissue from the control donor of the Netherlands Brain Bank was obtained (VU Medical Center ethic committee approval Reference number 2009/148)
Version history
- Received: April 29, 2019
- Accepted: August 1, 2019
- Accepted Manuscript published: August 1, 2019 (version 1)
- Version of Record published: August 23, 2019 (version 2)
Copyright
© 2019, Ramaglia 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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Multiplexed imaging of immune cells in staged multiple sclerosis lesions by mass cytometry
eLife 8:e48051.
https://doi.org/10.7554/eLife.48051
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