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前沿:肥大细胞调节多发性硬化症复发缓解模型中的疾病严重程度。

Cutting edge: mast cells regulate disease severity in a relapsing-remitting model of multiple sclerosis.

机构信息

Department of Microbiology and Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.

出版信息

J Immunol. 2011 Mar 15;186(6):3294-8. doi: 10.4049/jimmunol.1003574. Epub 2011 Feb 16.

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.

摘要

肥大细胞(MCs)对 C57BL/6(B6)品系依赖性实验性变态反应性脑脊髓炎(EAE),即原发性进行性多发性硬化症(MS)的模型中的疾病严重程度具有显著的病理影响。然而,用 SJL 小鼠模拟的复发缓解型 MS 更为普遍。鉴于不同品系小鼠的 MC 数量和反应性存在遗传决定的异质性,我们询问这些细胞是否也会影响这种更具临床相关性的 MS 模型。类似于市售的 WBB6F(1)-Kit(W/W-v) 小鼠,SJL-Kit(W/W-v) 小鼠是 MC 缺陷型、贫血和中性粒细胞减少症,并且具有正常的 T 细胞区室。它们表现出显著降低的疾病严重程度,但保留复发缓解的病程,这种表型可以通过选择性 MC 重建来逆转。这些数据证实,MC 的影响不仅局限于 EAE 的孤立模型,并揭示了一个新的系统来研究 MC 异质性对复发缓解型 EAE 和其他 SJL 品系特异性疾病的影响。

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