Increased severity of experimental allergic encephalomyelitis in lyn-/- mice in the absence of elevated proinflammatory cytokine response in the central nervous system
Increased severity of experimental allergic encephalomyelitis in lyn-/- mice in the absence of elevated proinflammatory cytokine response in the central nervous system
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DOI：
10.4049/jimmunol.168.6.3105
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发表时间：
2002-03-15
影响因子：
4.4
通讯作者：
Sriram, S
中科院分区：
文献类型：
--
作者：
Du, C;Sriram, S
lyn 是 src 激酶家族的成员，是 B 细胞中重要的信号分子。 lyn(-/-) 小鼠表现出过度活跃的 B-1 细胞和 IgM 高球蛋白血症。 lyn 对 T 细胞功能和 Th1 介导的炎症性疾病发展的作用尚不清楚。因此，我们研究了 lyn 基因破坏对实验性过敏性脑脊髓炎 (EAE) 发展的影响，EAE 是一种成熟的 Th1 介导的自身免疫性疾病。与野生型（WT）相比，用髓磷脂少突胶质细胞蛋白（MOG）p35-55免疫后，lyn（-/-）小鼠的EAE临床和病理严重程度评分更高。 lyn(-/-)小鼠中EAE严重程度的增加与CNS中促炎细胞因子产生的相应增加无关。患有 EAE 的 lyn(-/-) 小鼠表现出血清抗 IgM MOG Ab 水平高于 WT 小鼠，同时脊髓中补体 C5 及其受体 C5aR 的 mRNA 水平适度增加。从 MOG 免疫的 lyn(-/-) 小鼠转移血清使 WT 小鼠的 EAE 恶化，表明抗 MOG IgM Abs 在 EAE 中具有致病作用。这些观察结果强调了 lyn 在调节 Th1 介导的疾病中的潜在作用以及自身抗体和补体在 EAE 发展中的作用。
lyn, a member of the src kinase family, is an important signaling molecule in B cells. lyn(-/-) mice display hyperactive B-1 cells and IgM hyperglobulinemia. The role of lyn on T cell function and development of Th1-mediated inflammatory disease is not known. Therefore, we examined the effect of disruption of the lyn gene on the development of experimental allergic encephalomyelitis (EAE), a well-established Th1-mediated autoimmune disease. Following immunization with myelin oligodendrocyte protein (MOG) p35-55,lyn(-/-) mice had higher clinical and pathological severity scores of EAE when compared with wild type (WT). The increase in the severity of EAE in lyn(-/-) mice was not associated with a commensurate increase in the production of proinflammatory cytokines in the CNS. lyn(-/-) mice with EAE showed elevation in serum anti-IgM MOG Ab levels over that seen in WT mice, along with a modest increase in the mRNA levels of complement C5 and its receptor, C5aR, in the spinal cord. Transfer of serum from MOG-immunized lyn(-/-) mice worsened EAE in WT mice, suggesting a pathogenic role for anti-MOG IgM Abs in EAE. These observations underscore the potential role of lyn in regulation of Th1-mediated disease and the role of autoantibodies and complement in the development of EAE.