The interplay between T helper cells and brain barriers in the pathogenesis of multiple sclerosis

Gabriele Angelini; Alessandro Bani; Gabriela Constantin; Barbara Rossi

doi:10.3389/fncel.2023.1101379

The interplay between T helper cells and brain barriers in the pathogenesis of multiple sclerosis

Front Cell Neurosci. 2023 Feb 15:17:1101379. doi: 10.3389/fncel.2023.1101379. eCollection 2023.

Authors

Gabriele Angelini¹, Alessandro Bani¹, Gabriela Constantin^{1

2}, Barbara Rossi¹

Affiliations

¹ Department of Medicine, Section of General Pathology, University of Verona, Verona, Italy.
² The Center for Biomedical Computing (CBMC), University of Verona, Verona, Italy.

Abstract

The blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB) represent two complex structures protecting the central nervous system (CNS) against potentially harmful agents and circulating immune cells. The immunosurveillance of the CNS is governed by immune cells that constantly patrol the BCSFB, whereas during neuroinflammatory disorders, both BBB and BCSFB undergo morphological and functional alterations, promoting leukocyte intravascular adhesion and transmigration from the blood circulation into the CNS. Multiple sclerosis (MS) is the prototype of neuroinflammatory disorders in which peripheral T helper (Th) lymphocytes, particularly Th1 and Th17 cells, infiltrate the CNS and contribute to demyelination and neurodegeneration. Th1 and Th17 cells are considered key players in the pathogenesis of MS and its animal model, experimental autoimmune encephalomyelitis. They can actively interact with CNS borders by complex adhesion mechanisms and secretion of a variety of molecules contributing to barrier dysfunction. In this review, we describe the molecular basis involved in the interactions between Th cells and CNS barriers and discuss the emerging roles of dura mater and arachnoid layer as neuroimmune interfaces contributing to the development of CNS inflammatory diseases.

Keywords: T helper cells; adhesion molecules; blood–brain barrier; choroid plexus; meningeal inflammation; multiple sclerosis; neuroinflammation.

Publication types

Review

Grants and funding

This work was supported in part by the European Research Council (ERC) advanced grant number 695714 IMMUNOALZHEIMER and the ERC Proof of Concept grant numbers 693606 IMPEDE and 101069397 NeutrAD, the National Recovery and Resilience Plan (PNRR), National Centers Program (National Biodiversity Future Center – NBFC), PNRR “Partenariati estesi” Program, grant MNESYS (to GC), and Fondazione Italiana Sclerosi Multipla (FISM), Genoa, Italy Project cod.2013/R/21 (to BR).