溶酶体自我稳定通路对中性粒细胞胞外陷阱（NETs）形成的调控效应及机制

The formation of neutrophil extracellular traps (NETs) is a danger signals that lead to induce autoantigen production and innate immune response. To clarify the regulatory mechanism will provide new strategies for the diagnosis and treatment of a variety of autoimmune diseases. The aim of this project is to explore targets and mechanism of regulating the formation of neutrophil extracellular traps. In our obtained preliminary results, we found that the information of neutrophil extracellular traps was interferenced with the change of lysosome, and there have the consistency of the time and location between the change of lysosome and the formation of NETs. Due to the self-stable of lysosome mainly depends on the membrane stability and ion transport. Thus, based on the previous research，in order to investigate the expression of the neutrophil biology function regulated by the change of lysosome and the regulatory mechanism to NETs which come from the lysosome through the pathway of lysosome self-stable—ATP acidification and calcium transportation, we set out to investigate the phenomenon that the change of lysosome impact the information of NETs . Furture, to clarify that the role and regulatory mechanism of lysosome during the information of NETs make a signification contribution to find out some conditions of the NETs information in autoimmune diseases. Meanwhile, it will provide theoretical and experimental basis to discover the new potential therapeutic target of autoimmune diseases.

中性粒细胞受外界刺激后可产生胞外陷阱（NETs）介导炎症反应。NETs的形成可诱导自身抗体产生、机体免疫应答，从而引起自身免疫性疾病的发生。阐明调节NETs形成的机制和靶点对炎症反应的调控及揭示自身免疫疾病发病机制有重要的意义前期工作中，课题组发现改变中性粒细胞溶酶体功能可影响NETs形成，溶酶体功能和形态的变化与NETs形成具有时间和位置的一致性。本课题旨在从溶酶体的自我稳定依赖的膜稳定性及离子转运角度探索NETs形成的靶点和调控机制。课题组将在既往研究基础上进一步探讨溶酶体功能改变对中性粒细胞生物学功能的影响，以及溶酶体通过自我稳定通路(ATP酸化通路和钙离子转运通路)对NETs形成的调控机制。从而阐明溶酶体对NETs形成的调控作用及机制，为发现炎症反应的调控因素及自身免疫性疾病潜在的治疗靶点提供理论和实验依据。