Kit (W-sh) mice develop earlier and more severe experimental autoimmune encephalomyelitis due to absence of immune suppression.
Kit (W-sh) mice develop earlier and more severe experimental autoimmune encephalomyelitis due to absence of immune suppression.
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DOI：
10.4049/jimmunol.1003603
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发表时间：
2011-07-01
期刊：
影响因子：
--
通讯作者：
Rostami A
中科院分区：
文献类型：
--
作者：
Li H;Nourbakhsh B;Safavi F;Li K;Xu H;Cullimore M;Zhou F;Zhang G;Rostami A
肥大细胞（MCs）一直被认为在自身免疫性疾病的发展中起致病作用，包括实验性自身免疫性脑脊髓炎（EAE）， ms的动物模型。然而，这些细胞的免疫调节功能最近被提出。我们利用MC缺乏的W-sh小鼠品系研究了MCs在EAE中的作用。W-sh小鼠出现更早、更严重的临床和病理疾病，伴有广泛的脱髓鞘和中枢神经系统炎症。炎症细胞主要由CD4+ T细胞、单核/巨噬细胞、中性粒细胞和树突状细胞（dc）组成。与野生型小鼠相比，mc缺陷小鼠CD4+ T细胞上MCP-1/CCR2和CD44的表达水平升高，Treg、IL-4、IL-5、IL-27和IL-10的表达减少。我们还发现，与野生型小鼠相比，免疫W-sh小鼠外周血淋巴细胞中IL-17、IFN-γ和GM-CSF水平显著升高。W-sh小鼠的重组下调了EAE的易感性，这与中枢神经系统的MC募集和Treg细胞活化有关。这些发现表明，中枢神经系统炎症性脱髓鞘的发病机制不需要反应性，在MCs缺失的情况下，MCP-1、CCR2、IL-17、IFN-γ、CD44等炎症分子的增加可能是EAE严重程度增加的原因。
Mast cells (MCs) have been thought to play a pathogenic role in the development of autoimmune diseases, including experimental autoimmune encephalomyelitis (EAE), an animal model of MS. However, an immunoregulatory function of these cells has been recently suggested. We investigated the role of MCs in EAE using the W-sh mouse strain, which is MC deficient. W-sh mice developed earlier and more severe clinical and pathological disease, with extensive demyelination and inflammation in the CNS. The inflammatory cells were mainly comprised of CD4+ T cells, monocyte/macrophages, neutrophils and dendritic cells (DCs). Compared to wild-type mice, MC-deficient mice exhibited an increased level of MCP-1/CCR2, and CD44 expression on CD4+ T cells, in addition to decreased production of Treg, IL-4, IL-5, IL-27 and IL-10. We also found that levels of IL-17, IFN-γ, and GM-CSF were significantly increased in peripheral lymphocytes from immunized W-sh mice compared with wild-type mice. Reconstitution of W-sh mice downregulated susceptibility to EAE, which correlated with MC recruitment and Treg cells activation in the CNS. These findings indicate that responsiveness is not required in the pathogenesis of inflammatory demyelination in the CNS, and that, in the absence of MCs, increased MCP-1, CCR2, IL-17, IFN-γ, CD44 and other inflammatory molecules may be responsible for increased severity of EAE.
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影响因子：
64.8
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