B细胞参与非酒精性脂肪性肝病致病过程的研究

Both innate and adaptive immune factors had been proven to contribute to the pathogenesis of non-alcoholic fatty liver disease (NAFLD).Although innate immune cells and T lymphocytes had been extensively studied, little was known about the roles of B lymphocytes in NAFLD. B lymphocytes participate in the progression of metabolic syndrome. What’s more, our previous studies found that B lymphocytes increased in the high-fat diet induced NAFLD mice and the intrahepatic B lymphocytes promoted inflammation in NAFLD. Therefore, we proposed that B lymphocytes altered in NAFLD patients as well. This present study aims to investigate the alterations and mechanisms of B lymphocytes in NAFLD patients. Evidences of the pathogenic mechanisms will be provied by both experiments in vitro and in μMT(B-null) mice. Meanwhile, we will analyze the relationship between the NAFLD satges and B lymphocyte's property.

目前研究表明固有免疫及适应性免疫均参与了非酒精性脂肪性肝病（non-alcoholic fatty liver disease，NAFLD）的发病，但重点集中固有免疫及T细胞在NAFLD发病中的作用，关于NAFLD发生时B细胞变化和功能的研究鲜见。而B细胞在肥胖、胰岛素抵抗、2型糖尿病等代谢综合征的作用已经得到证实。同时，申请人前期的研究发现高脂饮食诱导NAFLD小鼠体内B细胞增多并且其肝脏内B细胞通过促进炎症参与了NAFLD发生。由此推测，NAFLD患者B细胞的数量和功能也存在一定的变化。因此本项研究拟通过检测NAFLD患者外周血B细胞的数量、功能等变化以明确B细胞在NAFLD中的作用，并通过体外细胞实验及动物实验研究NAFLD患者B细胞功能变化的原因。同时将通过比较不同疾病程度阶段NAFLD患者B细胞的特性以探讨其在疾病进展中的作用。

非酒精性脂肪性肝病(non-alcoholic fatty liver disease, NAFLD)是我国越来越常见的慢性肝病，多项研究提示免疫因素参与其中，但既往研究多集中于固有免 疫细胞和T淋巴细胞的作用方面，关于B细胞与NAFLD的研究较少。本项研究通过检测NAFLD患者外周血B细胞的数量、功能等变化以明确B细胞在NA FLD中的作用，并通过体外细胞实验及动物实验研究进行了证实。 .本研究发现NAFLD患者存在B淋巴细胞比例升高，其血浆促进B淋巴细胞的活化及分化的细胞因子含量增高。NAFLD患者B细胞分泌促炎性细胞因子及抑炎性细胞因子水平均升高。血浆免疫球蛋白中IgA及IgE增多，而IgM减少。同时课题组通过高脂饮食喂养、回输B淋巴细胞等实验，证明B细胞缺陷的NAFLD小鼠肝脏炎症水平、脂肪化程度均较野生型NAFLD小鼠减轻，表明B淋巴细胞促进了NAFLD的进展。而过继回输实验提示B细胞能够迁移至肝内促进炎症反应。.综上，我们的研究提示B淋巴细胞通过多种复杂的途径参与了NAFLD，其中促炎因素和抑炎因素相互作用的失衡可能最终导致了NAFLD的发生。这为未来治疗NAFLD提供了思路。..