Gaur Pratibha, Cebula Marcin, Riehn Mathias, Hillebrand Upneet, Hauser Hansjörg, Wirth Dagmar
Model Systems for Infection and Immunity, Helmholtz Centre for Infection Research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Model Systems for Infection and Immunity, Helmholtz Centre for Infection Research, Inhoffenstr. 7, 38124 Braunschweig, Germany; Institute for Experimental Hematology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany.
Metabolism. 2017 Apr;69:171-176. doi: 10.1016/j.metabol.2017.01.022. Epub 2017 Jan 20.
Obesity is accompanied with systemic inflammation and pre-conditions to severe alterations in liver environment and functions. So far, it remains elusive to which extent obesity modulates immune responses during hepatotropic virus infections as well as in autoimmune hepatitis. In this study we investigated the influence of obesity on the intrahepatic immune response, in particular on the function of CD8 T cells as the crucial players in clearance of virus infected hepatocytes.
We established high fat induced obesity in transgenic mouse models with hepatocyte specific expression of a model antigen (Ova). We investigated the immune response upon adoptive transfer of antigen specific T cells and in mice with continuous thymic output of antigen specific T cells, mimicking the situations upon acute infection and autoimmunity, respectively.
Irrespective of the metabolic condition, adoptive T cell transfer resulted in a transient hepatitis with no obvious differences concerning the acute T cell response. In the situation of autoimmunity, we observed a transient hepatitis in lean mice, whereas an extended hepatitis with a reduced antigen clearance capacity was found in obese mice.
Our results demonstrate that obesity affects T cell function and increases the severity of autoimmune hepatitis while it has no impact on the acute T cell response.
肥胖伴随着全身炎症，并为肝脏环境和功能的严重改变创造了前提条件。迄今为止，肥胖在嗜肝病毒感染以及自身免疫性肝炎期间对免疫反应的调节程度仍不清楚。在本研究中，我们调查了肥胖对肝内免疫反应的影响，特别是对作为清除病毒感染肝细胞关键因素的CD8 T细胞功能的影响。
我们在具有模型抗原（卵清蛋白）肝细胞特异性表达的转基因小鼠模型中建立了高脂肪诱导的肥胖。我们分别研究了抗原特异性T细胞过继转移后的免疫反应，以及在具有抗原特异性T细胞持续胸腺输出的小鼠中的免疫反应，分别模拟急性感染和自身免疫时的情况。
无论代谢状况如何，过继T细胞转移都会导致短暂性肝炎，急性T细胞反应无明显差异。在自身免疫情况下，我们在瘦小鼠中观察到短暂性肝炎，而在肥胖小鼠中发现了具有降低的抗原清除能力的持续性肝炎。
我们的结果表明，肥胖会影响T细胞功能并增加自身免疫性肝炎的严重程度，而对急性T细胞反应没有影响。
