Multiplex immunohistochemistry of chronic active multiple sclerosis lesions links fibroblast-associated vessels with immune cell cuffs

Multiple sclerosis (MS) is a chronic neurodegenerative disorder characterized by inflammatory demyelinating lesions affecting the brain, optic nerve, and spinal cord. Recent studies have revealed a heterogeneous population of PDGFRβ+ cells in MS lesions, comprising both pericytes and perivascular fibroblasts. However, their spatial distribution and relationship to chronic inflammation remain poorly understood.

To address this gap, researchers employed multiplex immunohistochemistry to analyze the spatial localization of fibroblasts, pericytes, and immune cells in MS lesions. The study examined 17,633 vessels across 5 control white matter samples, 5 normal-appearing white matter samples, 4 active MS lesions, and 4 chronic active MS lesions. The findings revealed that while the number of vessels remained unchanged in MS lesions, the perivascular space area was significantly increased.

By analyzing publicly available sequencing datasets, the researchers confirmed COL1A1 and SLC6A12 as markers for fibroblasts and pericytes, respectively, in the human brain. Unsupervised clustering of PDGFRβ, COL1A1, and SLC6A12 expression profiles in individual vessels distinguished three partially overlapping vessel clusters. The fibroblast-associated vessel type (high COL1A1, low SLC6A12) was found to be more prevalent in the rim and center of chronic active lesions.

Importantly, the fibroblast-associated vessels were associated with increased perivascular space enlargement and greater accumulation of immune cells in chronic active lesions. These findings provide a spatial link between perivascular fibroblasts and chronic inflammation in MS, suggesting that fibroblast-associated vessels play a crucial role in the development of immune cell cuffs in MS lesions.