Vonghia Luisa, Ruyssers Nathalie, Schrijvers Dorien, Pelckmans Paul, Michielsen Peter, De Clerck Luc, Ramon Albert, Jirillo Emilio, Ebo Didier, De Winter Benedicte, Bridts Chris, Francque Sven
Department of Gastroenterology and Hepatology, Antwerp University Hospital, 2560 Antwerp, Belgium ; Department of Basic Medical Sciences, Neuroscience and Sensory Organs, University of Bari, 70100 Bari, Italy.
Laboratory of Experimental Medicine and Paediatrics, Division of Gastroenterology, University of Antwerp, 2560 Antwerp, Belgium.
Mediators Inflamm. 2015;2015:239623. doi: 10.1155/2015/239623. Epub 2015 Jul 1.
Inflammatory mediators that cross-talk in different metabolically active organs are thought to play a crucial role in the pathogenesis of Nonalcoholic Steatohepatitis (NASH). This study was aimed at investigating the CD4+RORγt+ T-helper cells and their counterpart, the CD4+CD25+FOXP3+ regulatory T cells in the liver, subcutaneous adipose tissue (SAT), and abdominal adipose tissue (AAT) in a high fat diet (HFD) mouse model.
C57BL6 mice were fed a HFD or a normal diet (ND). Liver enzymes, metabolic parameters, and liver histology were assessed. The expression of CD4+RORγt+ cells and regulatory T cells in different organs (blood, liver, AAT, and SAT) were analyzed by flow cytometry. Cytokine and adipokine tissue expression were studied by RT-PCR.
Mice fed a HFD developed NASH and metabolic alterations compared to normal diet. CD4+RORγt++ cells were significantly increased in the liver and the AAT while an increase of regulatory T cells was observed in the SAT of mice fed HFD compared to ND. Inflammatory cytokines were also upregulated.
CD4+RORγt++ cells and regulatory T cells are altered in NASH with a site-specific pattern and correlate with the severity of the disease. These site-specific differences are associated with increased cytokine expression.
在不同代谢活跃器官中相互作用的炎症介质被认为在非酒精性脂肪性肝炎（NASH）的发病机制中起关键作用。本研究旨在调查高脂饮食（HFD）小鼠模型肝脏、皮下脂肪组织（SAT）和腹部脂肪组织（AAT）中的CD4+RORγt+辅助性T细胞及其对应物CD4+CD25+FOXP3+调节性T细胞。
给C57BL6小鼠喂食高脂饮食或正常饮食（ND）。评估肝脏酶、代谢参数和肝脏组织学。通过流式细胞术分析不同器官（血液、肝脏、AAT和SAT）中CD4+RORγt+细胞和调节性T细胞的表达。通过RT-PCR研究细胞因子和脂肪因子的组织表达。
与正常饮食相比，喂食高脂饮食的小鼠发生了NASH和代谢改变。与正常饮食组相比，高脂饮食喂养的小鼠肝脏和AAT中CD4+RORγt++细胞显著增加，而SAT中调节性T细胞增加。炎症细胞因子也上调。
NASH中CD4+RORγt++细胞和调节性T细胞发生改变，具有位点特异性模式，且与疾病严重程度相关。这些位点特异性差异与细胞因子表达增加有关。
