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Updated: Jan 21, 2026
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
The landscape of myeloid and astrocyte phenotypes in acute multiple sclerosis lesions
Calvin Park1, Gerald Ponath1, Maya Levine-Ritterman1
1Department of Neurology, Yale School of Medicine, 300 George Street, Suite 353I, New Haven, CT, 06511, USA.
Abstract:
Activated myeloid cells and astrocytes are the predominant cell types in active multiple sclerosis (MS) lesions. Both cell types can adopt diverse functional states that play critical roles in lesion formation and resolution. In order to identify phenotypic subsets of myeloid cells and astrocytes, we profiled two active MS lesions with thirteen glial activation markers using imaging mass cytometry (IMC), a method for multiplexed labeling of histological sections. In the acutely demyelinating lesion, we found multiple distinct myeloid and astrocyte phenotypes that populated separate lesion zones. In the post-demyelinating lesion, phenotypes were less distinct and more uniformly distributed. In both lesions cell-to-cell interactions were not random, but occurred between specific glial subpopulations and lymphocytes. Finally, we demonstrated that myeloid, but not astrocyte phenotypes were activated along a lesion rim-to-center gradient, and that marker expression in glial cells at the lesion rim was driven more by cell-extrinsic factors than in cells at the center. This proof-of-concept study demonstrates that highly multiplexed tissue imaging, combined with the appropriate computational tools, is a powerful approach to study heterogeneity, spatial distribution and cellular interactions in the context of MS lesions. Identifying glial phenotypes and their interactions at different lesion stages may provide novel therapeutic targets for inhibiting acute demyelination and low-grade, chronic inflammation.
Insights
Activated myeloid cells and astrocytes exhibit diverse phenotypes within multiple sclerosis (MS) lesions. Imaging mass cytometry revealed distinct glial subpopulations and interactions, offering potential therapeutic targets for MS.
Area of Science:
- Neuroimmunology
- Cellular Biology
- Pathology
Background:
- Activated myeloid cells and astrocytes are key players in multiple sclerosis (MS) lesion development and resolution.
- These glial cells display diverse functional states influencing disease progression.
- Understanding glial heterogeneity is crucial for developing targeted MS therapies.
Purpose of the Study:
- To identify distinct phenotypic subsets of myeloid cells and astrocytes in active MS lesions.
- To investigate the spatial distribution and cell-to-cell interactions of glial subpopulations.
- To explore glial activation gradients within MS lesions.
Main Methods:
- Utilized imaging mass cytometry (IMC) to profile thirteen glial activation markers in two active MS lesions.
- Applied computational tools to analyze multiplexed histological data.
- Examined spatial relationships and cellular interactions between glial cells and lymphocytes.
Main Results:
- Identified multiple distinct myeloid and astrocyte phenotypes in an acutely demyelinating lesion, segregated by lesion zones.
- Observed less distinct and more uniform glial phenotypes in a post-demyelinating lesion.
- Demonstrated non-random cell-to-cell interactions between specific glial subpopulations and lymphocytes.
- Revealed a lesion rim-to-center gradient of myeloid cell activation, influenced by extrinsic factors at the rim.
Conclusions:
- Highly multiplexed tissue imaging combined with computational analysis is effective for studying MS lesion heterogeneity and cellular interactions.
- Distinct glial phenotypes and their spatial organization provide insights into MS pathogenesis.
- Identifying specific glial subpopulations and their interactions may lead to novel therapeutic strategies for MS.
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