The imbalance of Th17/Treg cells is involved in the progression of nonalcoholic fatty liver disease in mice

Abstract

BackgroundNon-alcoholic fatty liver disease (NAFLD) is a common, chronic liver disease worldwide. Recent studies have shown that T helper (Th) 17 and regulatory T (Treg) cells play critical roles in various disorders of liver inflammation. Here, we explored the value of polyene phosphatidylcholine capsules (PPC) for regulating the imbalance of Th17/Treg cells in the pathogenesis of mice with NAFLD.MethodsC57BL/6 mice were randomly divided into three groups as follows:normal diet (ND), high-fat diet (HF),and HF plus PPC(HF + PPC). The frequencies of splenic Th17 and Treg cells were measured by flow cytometry, and their related cytokines were analyzed by CBA and real-time PCR.ResultsAt the end of 24 weeks, mice in the HF group had a higher frequency of intrahepatic Th17 cells,and a lower proportion of Treg cells compared with the ND group. The levels of Th17 cell-related cytokines (IL-6, IL-17 and IL-23) in serum and in liver tisse were increased,and the hepatic mRNA levels of RORγt, STAT3 and IL-6 were also increased. By contrast,the FoxP3 mRNA level was decreased in the HF group. Moreover, significant pathological and biochemical changes in the liver, as well as serum biochemical changes, were found in mice with NAFLD. Interestingly, following treatment with PPC, the levels of liver inflammation,frequencies of Th17/Treg cells and associated cytokines,and biochemical data were significantly altered.ConclusionThese findings demonstrate a critical role for PPC in partially attenuating liver inflammatory responses in mice with NAFLD that involves the imbalance of Treg/Th17 cells and associated cytokines.

Interleukin‐23 promotes intestinal T helper type17 immunity and ameliorates obesity‐associated metabolic syndrome in a murine high‐fat diet model

“…Notably, HFD‐fed mice lacking IL‐23 also have more hepatic steatosis and exhibited a significant increase in triglyceride levels when compared with WT mice. In this context, a study demonstrated a correlation between increased levels of Th17 cell‐related cytokines, including IL‐6, IL‐17 and IL‐23, in hepatic tissue and significant pathological and biochemical changes in the liver . Overall, these data indicate that IL‐23 deficiency predisposes to obesity and exacerbates the deposition of hepatic fat and dyslipidaemia.…”

Immunotherapy with oral administration of humanized anti-CD3 monoclonal antibody: a novel gut-immune system-based therapy for metaflammation and NASH

“…Also, interleukin (IL)-17 secretion exacerbates hepatic steatosis and inflammation, whereas IL-17 neutralization attenuates lipopolysaccharide (LPS)-induced liver injury. An imbalance of Th17/T reg cells is involved in the progression of NAFLD [18,19]. B cells play a role in NASH pathogenesis via T cell activation and proinflammatory cytokine secretion [17].…”

“…B cells play a role in NASH pathogenesis via T cell activation and proinflammatory cytokine secretion [17]. An imbalance of Th17/T reg cells is involved in the progression of NAFLD [18,19]. Both NK and NK T cells participate in the immune cascade leading to NASH [20].…”

Nonalcoholic Fatty Liver Disease: Pathogenesis and Treatment in Traditional Chinese Medicine and Western Medicine

“…e treatment of NASH patients with PPC can improve their liver function and lower blood lipids [132,133]. He et al observed that PPC intervention may partially attenuate the inflammatory response by adjusting the imbalance of 17/Treg cells, thus ameliorating the progression of NAFLD [134].…”