CD8⁺ T cell-mediated endotheliopathy is a targetable mechanism of neuro-inflammation in Susac syndrome.

ABSTRACT: Neuroinflammation is often associated with blood-brain-barrier dysfunction, which contributes to neurological tissue damage. Here, we reveal the pathophysiology of Susac syndrome (SuS), an enigmatic neuroinflammatory disease with central nervous system (CNS) endotheliopathy. By investigating immune cells from the blood, cerebrospinal fluid, and CNS of SuS patients, we demonstrate oligoclonal expansion of terminally differentiated activated cytotoxic CD8⁺ T cells (CTLs). Neuropathological data derived from both SuS patients and a newly-developed transgenic mouse model recapitulating the disease indicate that CTLs adhere to CNS microvessels in distinct areas and polarize granzyme B, which most likely results in the observed endothelial cell injury and microhemorrhages. Blocking T-

SUBMITTER: Gross CC 

PROVIDER: S-EPMC6920411 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature