Maggio Roberta, Viscomi Carmela, Andreozzi Paola, D'Ettorre Gabriella, Viscogliosi Giovanni, Barbaro Barbara, Gori Manuele, Vullo Vincenzo, Balsano Clara
Laboratory of Molecular Virology and Oncology, Francesco Balsano Foundation, Rome, Italy; Institute of Molecular Biology and Pathology, National Research Council, Rome, Italy.
Laboratory of Molecular Virology and Oncology, Francesco Balsano Foundation, Rome, Italy.
PLoS One. 2014 Dec 22;9(12):e112346. doi: 10.1371/journal.pone.0112346. eCollection 2014.
Hepatitis C virus (HCV) infection is associated with hepatic and extrahepatic manifestations, including immunological disorders. Chronic Hepatitis C (CHC) is often characterized by cholesterol and lipid metabolism alterations, leading to hepatic steatosis. Cholesterol metabolism, in fact, is crucial for the viral life cycle. Recent works described that a higher dietary cholesterol intake is associated with the progression of HCV-related liver disease. CHC patients have increased levels of T helper 17 (Th17)-cells, a lymphocytic population involved in the pathogenesis of liver inflammation and autoimmune hepatitis. The balance between Th17 and regulatory T (Treg) cells is crucial for chronic inflammation and autoimmunity. Th17-cell differentiation is deeply influenced by the activation LXRs, nuclear receptors modulating cholesterol homeostasis. Moreover, HCV may affect these nuclear receptors, and cholesterol metabolism, through both direct and indirect mechanisms. On these bases, we hypothesized that modulation of cholesterol levels through Normocaloric Low Cholesterol Diet (NLCD) may represent an innovative strategy to reduce the progression of HCV infection, through the modulation of peripheral Th17/Treg balance. To this end, we performed a pilot study to investigate whether a Normocaloric Low Cholesterol Diet may be able to modulate Th17/Treg balance in patients affected by chronic HCV infection. After 30 days of NLCD CHC patients showed a significant reduction in Th17 cells frequency, which correlated with strong reduction of IL-17 and IL-22 serum levels. At the same time, we appreciated an increase in the percentage of Treg cells, thus improving Treg/Th17 balance. Moreover, we observed an increased expression of LXRs and their target genes: SREBP-1c and ABCA-1. In conclusion, NLCD finely regulates Th17/Treg balance, improving immune system response in CHC patients. This study could pave the way for new treatments of CHC patients, suggesting that change in lifestyle could support the management of these patients, promoting well-being and possibly hindering disease progression.
ClinicalTrials.gov NCT02038387.
丙型肝炎病毒（HCV）感染与肝脏及肝外表现相关，包括免疫紊乱。慢性丙型肝炎（CHC）通常以胆固醇和脂质代谢改变为特征，导致肝脂肪变性。事实上，胆固醇代谢对病毒生命周期至关重要。近期研究表明，较高的膳食胆固醇摄入量与HCV相关肝病的进展有关。CHC患者辅助性T细胞17（Th17）水平升高，Th17是一种参与肝脏炎症和自身免疫性肝炎发病机制的淋巴细胞群体。Th17细胞与调节性T（Treg）细胞之间的平衡对于慢性炎症和自身免疫至关重要。Th17细胞分化受到肝脏X受体（LXRs）激活的深刻影响，LXRs是调节胆固醇稳态的核受体。此外，HCV可通过直接和间接机制影响这些核受体以及胆固醇代谢。基于这些，我们推测通过正常热量低胆固醇饮食（NLCD）调节胆固醇水平可能是一种创新策略，可通过调节外周Th17/Treg平衡来减少HCV感染的进展。为此，我们进行了一项初步研究，以调查正常热量低胆固醇饮食是否能够调节慢性HCV感染患者的Th17/Treg平衡。在NLCD饮食30天后，CHC患者的Th17细胞频率显著降低，这与IL-17和IL-22血清水平的大幅降低相关。同时，我们发现Treg细胞百分比增加，从而改善了Treg/Th17平衡。此外，我们观察到LXRs及其靶基因SREBP-1c和ABCA-1的表达增加。总之，NLCD可精细调节Th17/Treg平衡，改善CHC患者的免疫系统反应。这项研究可能为CHC患者的新治疗方法铺平道路，表明生活方式的改变可以支持这些患者的管理，促进健康并可能阻碍疾病进展。
ClinicalTrials.gov NCT02038387
