Involvement of SWAP-70 in proteolipid protein-induced experimental autoimmune encephalomyelitis

TL;DR

This study shows that inhibiting SWAP-70 in mice worsens symptoms of an MS-like disease, suggesting it may help control autoimmunity.

Contribution

The study reveals a novel role of SWAP-70 in suppressing autoimmunity through its effect on follicular B cells in an MS model.

Findings

SWAP-70 inhibition increased clinical EAE scores in mice.

SWAP-70 inhibition led to higher follicular B-cell ratios in lymph nodes.

SWAP-70 may suppress autoimmunity by inhibiting follicular B cells.

Abstract

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).

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.

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.

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.

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