Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan.
J Gastroenterol. 2010 Aug;45(8):859-67. doi: 10.1007/s00535-010-0218-4. Epub 2010 Mar 2.
BACKGROUND/AIMS: The magnitude of antigen-specific immunity was assessed in a murine model of nonalcoholic fatty liver diseases (NAFLD). Because antigen-specific immunity was diminished in NAFLD mice, the underlying mechanisms were evaluated through analysis of the functions of antigen-presenting dendritic cells (DC) and other immunocytes.
For 12 weeks, NAFLD mice received a high-fat (60%) and high-calorie (520 kcal/100 g) diet. C57BL/6 mice (controls) received a standard diet. NAFLD mice and control mice were immunized with hepatitis B vaccine containing hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg). Antibody to HBsAg (anti-HBs), HBsAg and HBcAg-specific cellular immune response and functions of whole spleen cells, T lymphocytes, B lymphocytes and spleen DCs of NAFLD and control mice were assessed in vitro.
Levels of anti-HBs and the magnitude of proliferation of HBsAg and HBcAg-specific lymphocytes were significantly lower in NAFLD mice than control mice (P < 0.05). The spleen cells of NAFLD mice produced significantly higher levels of inflammatory cytokines (P < 0.05) and exhibited significantly increased T cell proliferation compared with control mice (P < 0.05). However, the antigen processing and presenting capacities of spleen DCs were significantly decreased in NAFLD mice compared with control mice (P < 0.05). Palmitic acid, a saturated fatty acid, caused diminished antigen processing and presenting capacity of both murine and human DCs.
Nonalcoholic fatty liver disease mice exhibit decreased magnitudes of antigen-specific humoral and cellular immune responses. This effect is mainly, if not solely, due to impaired antigen processing and presentation capacities of DC.
背景/目的：在非酒精性脂肪性肝病（NAFLD）的小鼠模型中评估了抗原特异性免疫的程度。由于 NAFLD 小鼠的抗原特异性免疫减弱，因此通过分析抗原呈递树突状细胞（DC）和其他免疫细胞的功能来评估潜在机制。
在 12 周内，NAFLD 小鼠接受高脂肪（60％）和高热量（520 卡路里/ 100 克）饮食。 C57BL / 6 小鼠（对照）接受标准饮食。 NAFLD 小鼠和对照小鼠用含有乙型肝炎表面抗原（HBsAg）和乙型肝炎核心抗原（HBcAg）的乙型肝炎疫苗免疫。在体外评估 NAFLD 和对照小鼠的抗 HBsAg（抗-HBs），HBsAg 和 HBcAg 特异性细胞免疫反应以及整个脾细胞，T 淋巴细胞，B 淋巴细胞和脾 DC 的功能。
NAFLD 小鼠的抗-HBs 水平和 HBsAg 和 HBcAg 特异性淋巴细胞增殖的程度明显低于对照小鼠（P <0.05）。与对照小鼠相比，NAFLD 小鼠的脾细胞产生的炎症细胞因子水平明显更高（P <0.05），并且与对照小鼠相比，T 细胞增殖明显增加（P <0.05）。但是，与对照小鼠相比，NAFLD 小鼠的脾 DC 的抗原加工和呈递能力明显降低（P <0.05）。饱和脂肪酸棕榈酸会降低鼠和人 DC 的抗原加工和呈递能力。
非酒精性脂肪性肝病小鼠表现出抗原特异性体液和细胞免疫反应程度降低。这种作用主要（如果不是唯一的话）是由于 DC 的抗原加工和呈递能力受损所致。
