Division of Gastroenterology and Hepatology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Digestive Disease, Shanghai ,P.R.China.
PLoS One. 2013 Dec 3;8(12):e81949. doi: 10.1371/journal.pone.0081949. eCollection 2013.
Dietary lipids play an important role in the progression of non-alcoholic fatty liver disease (NAFLD) through alternation of liver innate immune response.
The present study was to investigate the effect of lipid on Kupffer cells phenotype and function in vivo and in vitro. And further to investigate the impact of lipid on ability of Kupffer cell lipid antigen presentation to activate NKT cells.
Wild type male C57BL/6 mice were fed either normal or high-fat diet. Hepatic steatosis, Kupffer cell abundance, NKT cell number and cytokine gene expression were evaluated. Antigen presentation assay was performed with Kupffer cells treated with certain fatty acids in vitro and co-cultured with NKT cells.
High-fat diet induced hepatosteatosis, significantly increased Kupffer cells and decreased hepatic NKT cells. Lipid treatment in vivo or in vitro induced increase of pro-inflammatory cytokines gene expression and toll-like receptor 4 (TLR4) expression in Kupffer cells. Kupffer cells expressed high levels of CD1d on cell surface and only presented exogenous lipid antigen to activate NKT cells. Ability of Kupffer cells to present antigen and activate NKT cells was enhanced after lipid treatment. In addition, pro-inflammatory activated Kupffer cells by lipid treatment induced hepatic NKT cells activation-induced apoptosis and necrosis.
High-fat diet increase Kupffer cells number and induce their pro-inflammatory status. Pro-inflammatory activated Kupfffer cells by lipid promote hepatic NKT cell over-activation and cell death, which lead to further hepatic NKT cell deficiency in the development of NAFLD.
膳食脂质通过改变肝脏固有免疫反应在非酒精性脂肪性肝病（NAFLD）的进展中起重要作用。
本研究旨在研究脂质对体内和体外库普弗细胞表型和功能的影响。并进一步研究脂质对库普弗细胞脂质抗原呈递激活 NKT 细胞能力的影响。
用正常或高脂肪饮食喂养野生型雄性 C57BL/6 小鼠。评估肝脂肪变性、库普弗细胞丰度、NKT 细胞数量和细胞因子基因表达。用特定脂肪酸体外处理库普弗细胞，并与 NKT 细胞共培养，进行抗原呈递试验。
高脂肪饮食诱导肝脂肪变性，显著增加库普弗细胞并减少肝 NKT 细胞。体内或体外脂质处理诱导库普弗细胞中促炎细胞因子基因表达和 Toll 样受体 4（TLR4）表达增加。库普弗细胞表面表达高水平的 CD1d，仅呈递外源性脂质抗原以激活 NKT 细胞。脂质处理后库普弗细胞呈递抗原和激活 NKT 细胞的能力增强。此外，脂质处理的促炎激活库普弗细胞诱导肝 NKT 细胞激活诱导的凋亡和坏死。
高脂肪饮食增加库普弗细胞数量并诱导其促炎状态。脂质激活的促炎库普弗细胞促进肝 NKT 细胞过度激活和细胞死亡，导致 NAFLD 发展过程中肝 NKT 细胞进一步缺乏。
