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Published on: July 19, 2019
Multiplexed imaging of immune cells in staged multiple sclerosis lesions by mass cytometry
Valeria Ramaglia1, Salma Sheikh-Mohamed1, Karen Legg1
1Department of Immunology, University of Toronto, Toronto, Canada.
Insights
Imaging mass cytometry (IMC) reveals detailed cellular differences in multiple sclerosis (MS) lesions. This advanced technique helps distinguish immune cells and understand their roles in MS pathology.
Area of Science:
- Neuroimmunology
- Cellular Biology
- Biomedical Imaging
Background:
- Multiple sclerosis (MS) involves demyelination and inflammation in the central nervous system, with lesion variability complicating research.
- Understanding the cellular composition of MS lesions is crucial for developing targeted therapies.
Observation:
- Imaging mass cytometry (IMC) was employed to simultaneously visualize over 15 proteins within distinct stages of MS lesions.
- A severe case of rebound MS disease activity post-natalizumab cessation was analyzed to test IMC's discriminatory power.
Findings:
- IMC successfully differentiated demyelinating macrophages from resident microglia.
- The study identified lymphocyte proximity to blood vessels and characterized multiple T and B cell subsets.
- Analysis revealed T cell phenotype dynamics relative to lesion type and location.
Implications:
- IMC offers a powerful tool for comprehensive single-cell analysis in MS.
- It enables detailed study of cell phenotypes, functional states, and interactions within the MS lesion microenvironment.
- This technology can advance our understanding of demyelinating activity and lesion progression in multiple sclerosis.
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.
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