Cutting edge: mast cells regulate disease severity in a relapsing-remitting model of multiple sclerosis
Blayne A Sayed1, Margaret E Walker, Melissa A Brown
1Department of Microbiology and Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Abstract:
Mast cells (MCs) exert a significant pathologic influence on disease severity in C57BL/6 (B6) strain-dependent experimental allergic encephalomyelitis (EAE), a model of primary progressive multiple sclerosis (MS). However, relapsing-remitting MS, which is modeled in SJL mice, is the more prevalent form. Given genetically determined heterogeneity in numbers and responsiveness of MCs from various strains of mice, we asked whether these cells also influence this more clinically relevant MS model using SJL-Kit(W/W-v) mice. Similar to the commercially available WBB6F(1)-Kit(W/W-v) mice, SJL-Kit(W/W-v) mice are MC-deficient, anemic, and neutropenic and have normal T cell compartments. They exhibit significantly reduced disease severity, but retain the relapsing-remitting course, a phenotype reversed by selective MC reconstitution. These data confirm that MC influence is not confined to an isolated model of EAE and reveal a new system to study the effects of MC heterogeneity on relapsing-remitting EAE and other SJL strain-specific diseases.
Insights
Mast cells significantly impact experimental allergic encephalomyelitis (EAE) severity in SJL mice, a model for relapsing-remitting multiple sclerosis (MS). Reducing mast cells lessened disease severity, demonstrating their crucial role in this MS model.
Area of Science:
- Immunology
- Neuroscience
- Pathology
Background:
- Mast cells (MCs) are implicated in the pathology of experimental allergic encephalomyelitis (EAE) in C57BL/6 mice.
- Relapsing-remitting multiple sclerosis (MS) is more prevalent than primary progressive MS and is modeled in SJL mice.
- Genetic variations in mouse strains affect mast cell numbers and responsiveness.
Purpose of the Study:
- To investigate the role of mast cells in the SJL mouse model of relapsing-remitting MS.
- To determine if mast cell deficiency influences disease severity and course in this model.
- To explore the potential of SJL-Kit(W/W-v) mice for studying mast cell heterogeneity in EAE.
Main Methods:
- Utilized SJL-Kit(W/W-v) mice, which are deficient in mast cells.
- Compared disease severity and course in mast cell-deficient SJL mice versus control mice.
- Reconstituted mast cells selectively in SJL-Kit(W/W-v) mice to observe phenotypic reversal.
Main Results:
- SJL-Kit(W/W-v) mice exhibited significantly reduced EAE disease severity.
- The relapsing-remitting course of EAE was maintained in mast cell-deficient mice.
- Selective mast cell reconstitution reversed the reduced disease severity phenotype.
Conclusions:
- Mast cell influence on EAE is not limited to specific mouse models.
- Mast cells play a critical role in the pathogenesis of relapsing-remitting EAE in SJL mice.
- SJL-Kit(W/W-v) mice provide a valuable model for studying mast cell heterogeneity in MS and other SJL strain-specific diseases.
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