Mast cells are essential for early onset and severe disease in a murine model of multiple sclerosis.
Mast cells are essential for early onset and severe disease in a murine model of multiple sclerosis.
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在多发性硬化症的鼠模型中，肥大细胞对于早期发作和严重疾病至关重要。
DOI：
10.1084/jem.191.5.813
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发表时间：
2000-03-06
影响因子：
15.3
通讯作者：
Brown, M A
中科院分区：
文献类型：
--
作者：
Secor, V H;Secor, W E;Gutekunst, C A;Brown, M A
除了它们在过敏性炎症中的充分表征的作用之外，最近的数据证实肥大细胞在各种免疫应答中发挥更广泛的作用。然而，它们对自身免疫性和神经系统疾病过程的贡献尚未被研究。实验性变态反应性脑脊髓炎（EAE）及其人类疾病对应物多发性硬化症被认为是影响中枢神经系统的CD 4 + T细胞介导的自身免疫性疾病。一些间接证据表明，肥大细胞也可能在人类和小鼠疾病的发病机制中发挥作用。使用髓磷脂少突胶质细胞糖蛋白（MOG）诱导的急性EAE模型，我们发现，肥大细胞缺陷的W/Wv小鼠表现出显着降低疾病的发病率，延迟发病，并降低平均临床评分时，与野生型同类同窝。在两组之间未观察到MOG特异性T和B细胞应答的差异，表明W/Wv动物中不存在整体T或B细胞缺陷。在W/Wv小鼠中肥大细胞群的重建将早期和严重疾病的诱导恢复到野生型水平，表明肥大细胞对于疾病的全面表现至关重要。这些数据为EAE的免疫破坏提供了一种新的机制，并表明肥大细胞在神经系统炎症中起着更广泛的作用。
In addition to their well characterized role in allergic inflammation, recent data confirm that mast cells play a more extensive role in a variety of immune responses. However, their contribution to autoimmune and neurologic disease processes has not been investigated. Experimental allergic encephalomyelitis (EAE) and its human disease counterpart, multiple sclerosis, are considered to be CD4+ T cell–mediated autoimmune diseases affecting the central nervous system. Several lines of indirect evidence suggest that mast cells could also play a role in the pathogenesis of both the human and murine disease. Using a myelin oligodendrocyte glycoprotein (MOG)-induced model of acute EAE, we show that mast cell–deficient W/Wv mice exhibit significantly reduced disease incidence, delayed disease onset, and decreased mean clinical scores when compared with their wild-type congenic littermates. No differences were observed in MOG-specific T and B cell responses between the two groups, indicating that a global T or B cell defect is not present in W/Wv animals. Reconstitution of the mast cell population in W/Wv mice restores induction of early and severe disease to wild-type levels, suggesting that mast cells are critical for the full manifestation of disease. These data provide a new mechanism for immune destruction in EAE and indicate that mast cells play a broader role in neurologic inflammation.