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RESEARCH PRODUCT

Functional characterization of the dural sinuses as a neuroimmune interface

Sandro Da MesquitaSandro Da MesquitaZach PapadopoulosRoss G. KossinaMaria Beatriz LopesTornike MamuladzeAndrea CugurraAndrea CugurraIgor SmirnovTaitea DykstraPeter O. BayguinovAntoine DrieuJasmin HerzKalil Alves De LimaJames A. J. FitzpatrickMorgan WallPetra Erdmann-gilmoreAndrea Francesca SalvadorJonathan KipnisSanja SvibenJustin RustenhovenWendy BakerMackenzie LemieuxQiang ZhangR. Reid TownsendMitsuhiro Kanamori

subject

MaleT-LymphocytesDura materCentral nervous systemAntigen-Presenting CellsCranial SinusesBiologyGeneral Biochemistry Genetics and Molecular BiologyMural cell03 medical and health sciences0302 clinical medicineImmune privilegemedicineAnimalsHomeostasisHumansAntigensCellular Senescence030304 developmental biologyAntigen Presentation0303 health sciencesMultiple sclerosisImmunityMeningesmedicine.diseaseAcquired immune systemResearch HighlightChemokine CXCL12Mice Inbred C57BLPhenotypeNeuroimmunologymedicine.anatomical_structureFemaleDura MaterStromal CellsNeuroscience030217 neurology & neurosurgery

description

Summary Despite the established dogma of central nervous system (CNS) immune privilege, neuroimmune interactions play an active role in diverse neurological disorders. However, the precise mechanisms underlying CNS immune surveillance remain elusive; particularly, the anatomical sites where peripheral adaptive immunity can sample CNS-derived antigens and the cellular and molecular mediators orchestrating this surveillance. Here, we demonstrate that CNS-derived antigens in the cerebrospinal fluid (CSF) accumulate around the dural sinuses, are captured by local antigen-presenting cells, and are presented to patrolling T cells. This surveillance is enabled by endothelial and mural cells forming the sinus stromal niche. T cell recognition of CSF-derived antigens at this site promoted tissue resident phenotypes and effector functions within the dural meninges. These findings highlight the critical role of dural sinuses as a neuroimmune interface, where brain antigens are surveyed under steady-state conditions, and shed light on age-related dysfunction and neuroinflammatory attack in animal models of multiple sclerosis.

yearjournalcountryeditionlanguage
2021-02-01Cell
https://doi.org/10.1016/j.cell.2020.12.040