# Interaction of brain endothelial cells with T cells: implications for progression and therapeutic strategies of multiple sclerosis

**Authors:** Yan Zhao, Dongqi Zhu

PMC · DOI: 10.3389/fneur.2026.1721076 · Frontiers in Neurology · 2026-02-19

## TL;DR

This paper reviews how brain endothelial cells and T cells interact in multiple sclerosis, contributing to disease progression and treatment challenges.

## Contribution

The paper systematically summarizes the mutual interactions between brain endothelial cells and T cells in MS and highlights new therapeutic strategies.

## Key findings

- Brain endothelial cells facilitate T cell activation and CNS infiltration by upregulating MHC molecules and chemokines.
- T cells modulate the immunoregulatory and barrier functions of brain endothelial cells through ligand interactions.
- Targeting interactions between brain endothelial cells and T cells may offer new therapeutic approaches for MS.

## Abstract

The dynamic interplay between brain endothelial cells (BECs) and T cells is a key event in the pathogenesis of multiple sclerosis (MS). This process allows the extravasation of T cells from the peripheral circulation into the central nervous system (CNS), thereby triggering neuroinflammation and tissue damage. In MS, activated BECs facilitate T cell activation, recruitment, and CNS infiltration by upregulating major histocompatibility complex (MHC) molecules, cell adhesion molecules (CAMs), and chemokines. In response, T cells interact with BECs by expressing corresponding ligands, thereby modulating the immunoregulatory and barrier functions of BECs. This cross-talk between BECs and T cells significantly increases the complexity of MS treatment. Therefore, this review systematically summarizes the mutually reinforcing interactions between BECs and T cells based on existing research and highlights recent therapeutic strategies for either BECs or T cells that show promise in achieving favorable outcomes for treating MS.

## Linked entities

- **Proteins:** HLA-C (major histocompatibility complex, class I, C)
- **Diseases:** multiple sclerosis (MONDO:0005301), MS (MONDO:0006861)

## Full-text entities

- **Genes:** TJP1 (tight junction protein 1) [NCBI Gene 7082] {aka ZO-1}, HLA-A (major histocompatibility complex, class I, A) [NCBI Gene 3105] {aka HLAA}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, CD86 (CD86 molecule) [NCBI Gene 397441], JAM2 (junctional adhesion molecule 2) [NCBI Gene 58494] {aka C21orf43, CD322, IBGC8, JAM-B, JAMB, PRO245}, CXCL12 (C-X-C motif chemokine ligand 12) [NCBI Gene 6387] {aka IRH, PBSF, SCYB12, SDF1, TLSF, TPAR1}, IFNB1 (interferon beta 1) [NCBI Gene 3456] {aka IFB, IFF, IFN-beta, IFNB}, ABCB1 (ATP binding cassette subfamily B member 1) [NCBI Gene 5243] {aka ABC20, CD243, CLCS, ENPAT, GP170, MDR1}, CDH5 (cadherin 5) [NCBI Gene 1003] {aka 7B4, CD144}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, CXCR4 (C-X-C motif chemokine receptor 4) [NCBI Gene 7852] {aka CD184, D2S201E, FB22, HM89, HSY3RR, LCR1}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, ITGA3 (integrin subunit alpha 3) [NCBI Gene 3675] {aka CD49C, FRP-2, GAP-B3, GAPB3, ILNEB, JEB7}, SELE (selectin E) [NCBI Gene 6401] {aka CD62E, ELAM, ELAM1, ESEL, LECAM2, selectin-e}, MCAM (melanoma cell adhesion molecule) [NCBI Gene 4162] {aka CD146, HEMCAM, METCAM, MUC18, MelCAM}, CXCR5 (C-X-C motif chemokine receptor 5) [NCBI Gene 643] {aka BLR1, CD185, MDR15}, ITGAL (integrin subunit alpha L) [NCBI Gene 3683] {aka CD11A, EV6, HNA-5, LFA-1, LFA1A}, TNF (tumor necrosis factor) [NCBI Gene 397086] {aka TNFSF2, TNFa}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, RHO (rhodopsin) [NCBI Gene 6010] {aka CSNBAD1, OPN2, RP4}, SELP (selectin P) [NCBI Gene 6403] {aka CD62, CD62P, GMP140, GRMP, LECAM3, PADGEM}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, CD274 (CD274 molecule) [NCBI Gene 574058] {aka PDL1}, VCAM1 (vascular cell adhesion molecule 1) [NCBI Gene 7412] {aka CD106, INCAM-100}, CD28 [NCBI Gene 100738615], CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, CD80 (CD80 molecule) [NCBI Gene 397161] {aka B7-1}, ALK (ALK receptor tyrosine kinase) [NCBI Gene 238] {aka ALK1, CD246, NBLST3}, IL17RA (interleukin 17 receptor A) [NCBI Gene 23765] {aka CANDF5, CD217, CDw217, IL-17RA, IL17R, IMD51}, F11R (F11 receptor) [NCBI Gene 50848] {aka CD321, JAM, JAM1, JAMA, JCAM, KAT}, IL17A (interleukin 17A) [NCBI Gene 3605] {aka CTLA-8, CTLA8, IL-17, IL-17A, IL17, ILA17}, CXCL10 (C-X-C motif chemokine ligand 10) [NCBI Gene 3627] {aka C7, IFI10, INP10, IP-10, SCYB10, crg-2}, MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318] {aka CLG4B, GELB, MANDP2, MMP-9}, CD86 (CD86 molecule) [NCBI Gene 942] {aka B7-2, B7.2, B70, BU63, CD28LG2, CD86 v6}, CCL21 (C-C motif chemokine ligand 21) [NCBI Gene 6366] {aka 6Ckine, CKb9, ECL, SCYA21, SLC, TCA4}, CD52 (CD52 molecule) [NCBI Gene 1043] {aka CDW52, EDDM5, HE5}, SELPLG (selectin P ligand) [NCBI Gene 6404] {aka CD162, CLA, PSGL-1, PSGL1}, CD4 (CD4 molecule) [NCBI Gene 404704], GSDMD (gasdermin D) [NCBI Gene 79792] {aka DF5L, DFNA5L, FKSG10, GSDMDC1}, RHOA (ras homolog family member A) [NCBI Gene 387] {aka ARH12, ARHA, EDFAOB, RHO12, RHOH12}, STAT1 (signal transducer and activator of transcription 1) [NCBI Gene 6772] {aka CANDF7, IMD31A, IMD31B, IMD31C, ISGF-3, STAT91}, CLDN5 (claudin 5) [NCBI Gene 7122] {aka AWAL, BEC1, CPETRL1, TMDVCF, TMVCF}, NR3C1 (nuclear receptor subfamily 3 group C member 1) [NCBI Gene 2908] {aka GCCR, GCR, GCRST, GR, GRL}, PGP (phosphoglycolate phosphatase) [NCBI Gene 283871] {aka AUM, G3PP, PGPase}, ACKR3 (atypical chemokine receptor 3) [NCBI Gene 57007] {aka CMKOR1, CXC-R7, CXCR-7, CXCR7, GPR159, RDC-1}, IL2RA (interleukin 2 receptor subunit alpha) [NCBI Gene 3559] {aka CD25, IDDM10, IL2R, IMD41, TCGFR, p55}, CD80 (CD80 molecule) [NCBI Gene 941] {aka B7, B7-1, B7.1, BB1, CD28LG, CD28LG1}, ICAM1 (intercellular adhesion molecule 1) [NCBI Gene 3383] {aka BB2, CD54, P3.58}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, MANEA (mannosidase endo-alpha) [NCBI Gene 79694] {aka ENDO, hEndo}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, IL22RA1 (interleukin 22 receptor subunit alpha 1) [NCBI Gene 58985] {aka CRF2-9, IL22R, IL22R1}, CXCR3 (C-X-C motif chemokine receptor 3) [NCBI Gene 2833] {aka CD182, CD183, CKR-L2, CMKAR3, GPR9, IP10-R}, CXCL13 (C-X-C motif chemokine ligand 13) [NCBI Gene 10563] {aka ANGIE, ANGIE2, BCA-1, BCA1, BLC, BLR1L}, HLA-C (major histocompatibility complex, class I, C) [NCBI Gene 3107] {aka D6S204, HLA-JY3, HLAC, HLC-C, MHC, PSORS1}, IL2RB (interleukin 2 receptor subunit beta) [NCBI Gene 3560] {aka CD122, IL15RB, IMD63, P70-75}, CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}, IFNG (interferon gamma) [NCBI Gene 396991], ST14 (ST14 transmembrane serine protease matriptase) [NCBI Gene 6768] {aka ARCI11, CAP3, HAI, MT-SP1, MTSP1, PRSS14}
- **Diseases:** tissue damage (MESH:D017695), BECs (MESH:D055954), axonal damage (MESH:D001480), endothelial (MESH:D005642), MS (MESH:D009103), BEC dysfunction (MESH:D006331), EAE (MESH:D004681), RRMS (MESH:D020529), Dysfunction of BECs (MESH:D002561), cytotoxic (MESH:D064420), T (MESH:D001260), brain inflammation (MESH:D004660), demyelination (MESH:D003711), PML (MESH:D007968), systemic sclerosis (MESH:D012595), neurological deficits (MESH:D009461), autoimmune disease (MESH:D001327), neuroinflammation (MESH:D000090862), BBB abnormalities (MESH:C536830), opportunistic infections (MESH:D009894), CNS inflammation (MESH:D007249)
- **Chemicals:** pyrimidine nucleotides (MESH:D011742), Natalizumab (MESH:D000069442), Teriflunomide (MESH:C527525), LPS (MESH:D008070), gadolinium (MESH:D005682), dexamethasone (MESH:D003907), Fingolimod (MESH:D000068876), Fasudil (MESH:C049347), Ocrelizumab (MESH:C533411), BEC (-), pyrimidine (MESH:C030986), hydrocortisone (MESH:D006854), Alemtuzumab (MESH:D000074323), Daclizumab (MESH:D000077561), Glatiramer acetate (MESH:D000068717)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** BEC — Mus musculus (Mouse), Hybridoma (CVCL_RQ14)

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12960123/full.md

## References

89 references — full list in the complete paper: https://tomesphere.com/paper/PMC12960123/full.md

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Source: https://tomesphere.com/paper/PMC12960123