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Turkish Journal of Medical Sciences

Abstract

Background/aim: Multiple sclerosis (MS) is a chronic demyelinating inflammatory disease of the central nervous system. Studies have shown that B cells may play an important role in the induction and progression of MS. Switch-associated protein 70 (SWAP-70) is a signal transduction molecule abundantly expressed in B cells and involved in B-cell polarization, directed migration, endothelial cell adhesion, and tissue homing. B-cell stimuli increase its expression. SWAP-70 has been implicated in the pathogenesis of autoimmune disorders, including MS. This study aims to investigate the effects of acquired SWAP-70 inhibition on immune cell subsets in experimental autoimmune encephalomyelitis (EAE).

Materials and methods: EAE was induced in Swiss James Lambert mice by immunization with proteolipid protein. EAE-induced mice were treated with either SWAP-70 short hairpin ribonucleic acid (shRNA) or nontargeting scrambled shRNA. Control PLP-immunized and non-PLP-immunized mice received saline treatment. The model was established by immunofluorescence studies demonstrating spinal cord demyelination and immune cell infiltration. Ratios of lymph node cell subsets were assessed by flow cytometry at termination.

Results: All PLP-immunized mice showed clinical signs of EAE and demyelination and CD8+ T-cell/macrophage infiltration at spinal cord sections. SWAP-70 shRNA-treated mice showed significantly higher average clinical EAE scores than the other groups. SWAP-70 shRNA-treated mice showed significantly higher lymph node CD19+CXCR5+CD21+ follicular B-cell ratios than other groups, whereas ratios of other effector B-cell and T-cell subsets were comparable among groups.

Conclusion: SWAP-70 appears to have an autoimmunity-suppressing effect in the PLP–EAE model, likely mediated by inhibiting follicular B cells. These findings propose a novel mechanism by which SWAP-70 might be involved in autoimmunity and endorse SWAP-70 as a potential target in novel MS-treatment strategies.

Author ORCID Identifier

CANAN ULUSOY: 0000-0002-5599-4917

GİZEM KORAL: 0000-0001-9484-9440

FATMA AKPUNAR SALMAN: 0000-0002-4715-2242

MELİS ŞEN: 0000-0002-3557-8203

EMİNE ŞEKERDAĞ KILIÇ: 0000-0002-4292-9761

RECAİ TÜRKOĞLU: 0000-0001-9724-851X

CEM İSMAİL KÜÇÜKALİ: 0000-0001-9851-8577

YASEMİN GÜRSOY ÖZDEMİR: 0000-0002-0860-8964

VUSLAT YILMAZ: 0000-0002-4809-2966

ERDEM TÜZÜN: 0000-0002-4483-0394

DOI

10.55730/1300-0144.6161

Keywords

autoimmunity, experimental autoimmune encephalomyelitis, follicular B cell, Multiple sclerosis, SWAP-70

First Page

274

Last Page

281

Publisher

The Scientific and Technological Research Council of Türkiye (TÜBİTAK)

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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