Signaling via immunoglobulin Fc receptors induces oligodendrocyte precursor cell differentiation
Signaling via immunoglobulin Fc receptors induces oligodendrocyte precursor cell differentiation
复制标题
DOI：
10.1016/s1534-5807(03)00155-2
复制
发表时间：
2003-06-01
影响因子：
11.8
通讯作者：
Asou, H
中科院分区：
文献类型：
--
作者：
Nakahara, J;Tan-Takeuchi, K;Asou, H
在少突胶质前体细胞（OPCs）分化为有髓鞘的少突胶质细胞的过程中，发生了形态和髓鞘蛋白表达的巨大变化。据报道，Fyn酪氨酸激酶在分化过程中发挥核心作用。尚未研究可诱导Fyn信号传导的分子。这些分子是脱髓鞘疾病中有希望的治疗靶点。我们提供的证据表明，免疫球蛋白Fc受体（FcRgamma）的共同γ链在OPCs中表达，并在触发Fyn信号传导中发挥作用。通过免疫球蛋白G在OPCs上的FcR γ交联促进Fyn信号传导的活化并诱导快速形态分化，同时上调髓鞘碱性蛋白（MBP）表达水平。FcR γ缺陷的小鼠是髓鞘化不足的，并且MBP含量的显著降低是明显的。我们的研究结果表明，FcRgamma-Fyn-MBP级联是关键的OPCs分化成髓鞘少突胶质细胞，揭示了一个意想不到的参与免疫分子。
Dramatic changes in morphology and myelin protein expression take place during the differentiation of oligodendrocyte precursor cells (OPCs) into myelinating oligodendrocytes. Fyn tyrosine kinase was reported to play a central role in the differentiation process. Molecules that could induce Fyn signaling have not been studied. Such molecules are promising therapeutic targets in demyelinating diseases. We provide evidence that the common gamma chain of immunoglobulin Fc receptors (FcRgamma) is expressed in OPCs and has a role in triggering Fyn signaling. FcRgamma cross-linking by immunoglobulin G on OPCs promotes the activation of Fyn signaling and induces rapid morphological differentiation with upregulation of myelin basic protein (MBP) expression levels. Mice deficient in FcRgamma are hypomyelinated, and a significant reduction in MBP content is evident. Our findings indicate that the FcRgamma-Fyn-MBP cascade is pivotal during the differentiation of OPCs into myelinating oligodendrocytes, revealing an unexpected involvement of immunological molecules.