Elucidation of the mechanisms underlying in the immunological abnormalities of lysosomal storage diseases

我们先前已经发现，在SD和hex-/-小鼠中诱导的神经系统疾病的进展与致病性抗糖脂自身抗体的产生有关。在这项研究中，我们聚焦于中枢神经系统的免疫异常。我们利用实时荧光定量聚合酶链式反应(Real-Time-PCR)技术监测了HexB-/-小鼠终末期的基因表达，发现与免疫反应相关的基因表达上调。B淋巴细胞趋化因子CXCL-13是上调表达的基因之一，在中枢神经系统中特异表达。为了确定CxCL-13的作用，还在Hexb-/-小鼠中破坏了cxCL-13基因，因为它在自身免疫性疾病中发挥了关键作用。与HexB-/-小鼠相比，HexB-/-、cxCL-13-/-小鼠的临床症状得到改善，寿命延长，神经细胞数量也增加。这些发现表明，CXCL-13的表达在神经病变的发病机制中起着重要作用，因此为新的治疗提供了靶点。

We have previously found that the progress neurologic disease induced in SD and hex-/- mice, is associated with the production of pathogenic anti-glycolipid autoantibodies. In this study, we focused immunological abnormalities in the CNS. We employed Real-time PCR analysis to monitor gene expression in the terminal stage of hexb-/- mice and found that gene associated with the immune responses were up-regulated. B lymphocyte chemoattractant CXCL-13 was one of there up-regulated genes and is expressed specifically in the CNS. To determine the role of the CXCL-13, the cxcl-13 gene was additionally disrupted in hexb-/- mice, as it play a key role in the autoimmune disease. Clinical symptoms were improved and life spans were extended in the hexb-/-, cxcl-13-/- mice and the number of neuronal cells was also increased than hexb-/- mice. These findings suggest that the expression of CXCL-13 plays an important role in the pathogenesis of neuropathy in hexb-/- mice and therefore provides a target for novel therapies.