酒精性肝病（ALD）是世界范围内高发的重大慢性疾病之一，造成严重的社会和经济负担。NLRP6是炎症小体家族成员之一，在肠道炎症发生中具有重要作用，但其参与ALD的机制仍然不清楚。我们的前期研究表明，临床ALD病人肝细胞中NLRP6炎症小体表达水平稍微上升，且大部分蛋白发生了入核过程。体外模型中将其强制入核可以模拟脂肪变性的发生。本研究将通过生物化学、生物物理学、细胞生物学和小鼠模型实验来揭示肝细胞NLRP6炎症小体入核过程参与酒精性肝病发病进程的分子机制，鉴定直接结合NLRP6蛋白并将其拉入核的靶标蛋白NBP。本研究将有助于发掘ALD炎症发生的新分子机制，为ALD治疗提供可能的药物靶点。

Alcoholic liver disease (ALD) is one of the most prevailing chronic diseases in the world, which causing heavy socio-economic burdens. NLRP6 is a member of inflammasome whose critical roles have been investigated in gut inflammation. However, its function during ALD progression remains largely unknown. Our preliminary studies indicated that the expression level of NLRP6 was slightly up-regulated, and most NLRP6 proteins translocated into the nuclei in the liver sample of ALD patients. Forced nuclear translocation of NLRP6 also resembled typical steatosis in cultured hepatocytes. In this project, we plan to conduct biochemical, biophysical, cell biology, and mouse model studies to unveil the molecular mechanism of NLRP6 nuclear translocation in hepatocytes during ALD progression, and to identify the direct binding protein of NLRP6 which is responsible for its nuclear translocation. Such studies should be of great importance for the delineation of new mechanisms of ALD inflammation development and to provide possible novel drug therapy target of ALD.