内源性MHCⅠ类分子对海马神经元突起生长的影响

The role of endogenous MHCⅠon the outgrowth of hippocampal neurons

大量研究证实,在免疫细胞发育及免疫应答等过程中行使重要功能的免疫分子主要组织相容性复合体Ⅰ(MHCⅠ)类蛋白,在中枢神经系统神经元上有广泛表达,并与突触形成、精确突触连接的建立密切相关。为进一步探究MHCⅠ类分子在中枢神经系统中的功能,以体外培养小鼠海马神经元为对象,检测发现在海马神经元突起生长、突触形成前已有MHCⅠ类分子表达,推测其表达可能与神经元突起生长相关;通过特异性抗体阻断MHCⅠ类分子信号通路或敲除编码MHCⅠ类分子重链的基因,神经元突起数目显著增多;利用特异性抗体阻断在免疫系统中作为MHCⅠ类分子配体发挥作用的PirB分子信号通路,同样发现神经元突起数目显著增加。实验结果初步证实内源性表达MHCⅠ类分子具有限制海马神经元突起生长的功能,为深入研究MHCⅠ类分子在中枢神经系统的新功能及其作用机制奠定基础。

Accumulating evidence indicates that immune proteins major histocompatibility complex I(MHCⅠ)molecules are expressed by healthy neurons.Based on the study of related knockout animals,the neuronal MHCⅠmolecules have been proved to play important roles in synaptic formation,remodeling and plasticity,which are significantly different from their well-acknowledged immune functions.Using cultured hippocampal neurons,we show MHCⅠproteins are expressed before neurite outgrowth.Knockout of MHC class I in cultured neurons or blocking of MHCⅠmolecules by MHCⅠantibody increases the branch number of neurons.Blocking of pirB,which works with MHCⅠin immune system,mimics the phenotype of increased dendritic branching.Our results imply that endogenous MHCⅠplays a role in limiting the neurite outgrowth during the development of hippocampal neurons.