The landscape of myeloid and astrocyte phenotypes in acute multiple sclerosis lesions

Abstract

23Activated myeloid cells and astrocytes are the predominant cell types in acute multiple sclerosis (MS) lesions. The 24 polarization states of these cells play a critical role in lesion formation and resolution. To identify myeloid and 25 astrocyte subsets present during lesion development, we profiled the cellular composition of an acutely demyelinating 26 and an acute post-demyelinating MS lesion with thirteen immune markers, using imaging mass cytometry (IMC). In 27 the early demyelinating lesion, distinct myeloid and astrocyte phenotypes populated separate lesion zones and engaged 28 in specific interactions. In the late active lesion, phenotypes were less diverse and more uniformly distributed 29 throughout the lesion. Our study demonstrates that multiplexed tissue imaging, combined with new computational 30 tools, is a powerful approach to study cellular heterogeneity and spatial organization in MS lesions. Identifying glial 31 phenotypes and their key interactions at different lesion stages may elucidate novel therapeutic targets for inhibiting 32 acute demyelination and low-grade neuro-inflammation.

Mass Cytometry Imaging for the Study of Human Diseases—Applications and Data Analysis Strategies

“…However, similar to T1DM, dissecting the role of the immune system has been challenging, due to both difficulty obtaining samples and the lack of technologies to simultaneously characterize the repertoire, functional state and spatial location of lesion-associated immune cell populations (77–79). Accordingly, two recent pre-prints by Ramaglia et al and Park et al have utilized IMC to characterize the immune environment of post-mortem MS brain tissue which we discuss in this section (54, 55).…”

“…Park et al used a panel of 13 markers to perform a targeted examination of myeloid and astrocyte phenotypes in MS lesions (55). A key strength of this study is the employment of sophisticated computational tools which demonstrate both diversity and specific ordering of immune networks within MS lesions.…”

“…The sources of variation of cell markers are decomposed into intrinsic effects, environmental effects, and cell-cell interactions. SVCA was applied by Park et al to investigate how multiple sclerosis (MS) brain lesion environments influence variations in cell marker expression (55). They found that toward the center of a lesion, the relative influence of intrinsic and environmental effects increased, while the relative influence of cell-cell interactions had decreased.…”