4.6 Article

Cutting Edge: Mast Cells Regulate Disease Severity in a Relapsing-Remitting Model of Multiple Sclerosis

Journal

JOURNAL OF IMMUNOLOGY
Volume 186, Issue 6, Pages 3294-3298

Publisher

AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1003574

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Funding

  1. National Multiple Sclerosis Society [RG3104B]
  2. National Institutes of Health [NS047578, F31 NS054395, F31 NS068031-02]

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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. The Journal of Immunology, 2011, 186: 3294-3298.

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