Qin Shan-yu, Lu Dong-hong, Guo Xiao-yun, Luo Wei, Hu Bang-li, Huang Xiao-li, Chen Mei, Wang Jia-xu, Ma Shi-Jia, Yang Xian-wen, Jiang Hai-xing, Zhou You
Department of Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
Systems Immunity University Research Institute, Cardiff University School of Medicine, Heath Park, Cardiff, UK.
Sci Rep. 2016 Jan 5;6:18694. doi: 10.1038/srep18694.
T helper 9 (Th9) cells, a recently recognized Th cell subset, are involved in autoimmune diseases. We aimed to investigate the role of Th9/interleukin-9 (IL-9) in the pathogenesis of hepatic fibrosis. Th9 and Th17 cells were quantified in chronic hepatitis B (CHB) patients with hepatic fibrosis, HBV-associated liver cirrhosis (LC) patients and healthy controls (HC). The percentages of Th9 and Th17 cells, concentrations of IL-9 and IL-17, as well as expression of IL-17, TNF-α, IL-6, IL-4, IL-21, TGF-β1 and IFN-γ were significantly increased in plasma of CHB and LC patients compared with those in HC. Splenic Th9 and Th17 cells, plasma concentrations and liver expression of IL-9 and IL-17A were significantly elevated in mice with hepatic fibrosis compared with controls. Neutralization of IL-9 in mice ameliorated hepatic fibrosis, attenuated the activation of hepatic stellate cells, reduced frequencies of Th9, Th17 and Th1 cells in spleen, and suppressed expression of IL-9, IL-17A, IFN-γ, TGF-β1, IL-6, IL-4 and TNF-α in plasma and liver respectively. Our data suggest a deleterious role of Th9/IL-9 in increasing hepatic fibrosis and exacerbating disease endpoints, indicating that Th9/IL9 based immunotherapy may be a promising approach for treating hepatic fibrosis.
辅助性T细胞9（Th9）是最近才被认识的一种Th细胞亚群，参与自身免疫性疾病。我们旨在研究Th9/白细胞介素-9（IL-9）在肝纤维化发病机制中的作用。对患有肝纤维化的慢性乙型肝炎（CHB）患者、HBV相关肝硬化（LC）患者和健康对照（HC）的Th9和Th17细胞进行了定量分析。与HC相比，CHB和LC患者血浆中Th9和Th17细胞的百分比、IL-9和IL-17的浓度以及IL-17、TNF-α、IL-6、IL-4、IL-21、TGF-β1和IFN-γ的表达均显著增加。与对照组相比，肝纤维化小鼠脾脏中的Th9和Th17细胞、血浆中IL-9和IL-17A的浓度以及肝脏中的表达均显著升高。在小鼠中中和IL-9可改善肝纤维化，减弱肝星状细胞的激活，降低脾脏中Th9、Th17和Th1细胞的频率，并分别抑制血浆和肝脏中IL-9、IL-17A、IFN-γ、TGF-β1、IL-6、IL-4和TNF-α的表达。我们的数据表明Th9/IL-9在增加肝纤维化和加重疾病终点方面具有有害作用，这表明基于Th9/IL9的免疫疗法可能是治疗肝纤维化的一种有前景的方法。
