Elucidating the mechanism of myelination : FcRγ-Fyn-MBP stream is critical for the CNS myelination.

阐明中枢神经系统髓鞘形成的机制是治疗脱髓鞘疾病的最终需要。我们已经阐明了免疫球蛋白Fc受体（FcR γ）的γ链作为免疫系统的必需信号分子作为少突胶质细胞髓鞘生成的触发剂的机制。FcR γ信号除了导致少突胶质细胞的形态分化外，还导致Fyn酪氨酸激酶（Fyn）和髓鞘碱性蛋白（MBP）表达水平的上调。FcR γ缺陷的小鼠表现出严重的髓鞘生成障碍，类似于在Fyn或MBP缺陷的小鼠中观察到的缺陷。FcR γ -Fyn双缺陷小鼠的髓鞘形成和MBP水平均明显低于两种单突变小鼠，提示FcR γ -Fyn-MBP级联反应在髓鞘形成中起重要作用。我们还在少突胶质细胞中检测到免疫球蛋白G特异性Fc受体与FcR γ的表达，表明免疫球蛋白可能有助于髓鞘形成。在少突胶质细胞中Fyn的调节因子CD 45的表达表明该分子参与了所提出的机制。我们的研究结果揭示了大脑和参与髓鞘生成的免疫系统之间的新联系，引入了一种新的治疗途径，可能治愈脱髓鞘疾病。

Elucidation of the mechanism of CNS myelinogenesis is ultimately required to cure demyelinating disease. We have elucidated the mechanism whereby the γ chain of immunoglobulin Fc recepter(FcR γ ), an essential signaling molecule of the immune system, functions as a trigger for oligodendroglial myelinogenesis. FcR γ signaling results in the up-regulation of Fyn tyrosine kinase (Fyn) and myelin basic protein (MBP) expression levels, in addition to the morphological differentiation of oligodendroglia. Mice deficient in FcR γ demonstrate severely disturbed myelinogenesis, similar to the defect observed in mice deficient in either Fyn or MBP. FcR γ -Fyn double deficient mice exhibit severer hypomyelination and decrease in MBP than those of both single mutant mice, implying that FcR γ -Fyn-MBP cascade is indeed critical for the myelinogenesis. We have also detected expression of Fc recepters specific for immunoglobulin G in conjunction with FcR γ in oligodendroglia, suggesting immunogloblins may contribute to myelinogenesis. Expression of CD45, a regulator of Fyn, in oligodendroglia suggests the involvement of this molecule in the proposed mechanism. Our findings uncover a new connection between the brain and the immune system involved in myelinogenesis, introducing a novel therapeutic avenue leading to a possible cure for demyelinating disease.