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

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