Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Scand J Immunol. 2019 Aug;90(2):e12775. doi: 10.1111/sji.12775. Epub 2019 May 22.
Invariant NKT (iNKT) cells express markers of both T and NK cells and may produce various cytokines to regulate liver immunity. However, the role of iNKT cells in the progression of HBV-relative liver cirrhosis (HBV-LC) is incompletely understood. Here, we investigated the impact of peripheral iNKT cells on a cohort of patients with HBV-LC. The frequency, number, activation status, apoptosis and proliferation ability of peripheral iNKT cells were detected with flow cytometry. The impact of peripheral iNKT cells on the proliferation of hepatocyte cell line (MIHA) and activation of hepatic stellate cell line (LX-2) was detected with flow cytometry and PCR. In HBV-LC patients, the frequency and absolute number of peripheral iNKT cells significantly reduced, but the expression levels of CD25, interleukin (IL)-4, IL-13 and interferon (IFN)-γ increased. No difference was observed in the proliferation and apoptosis of circulating iNKT cells between patients and healthy controls (HCs). CXCR6 (CD186), known to be closely associated with iNKT cells migration from the periphery to the liver, was highly expressed on peripheral iNKT cells in HBV-LC patients. Furthermore, peripheral iNKT cells had a profound impact on MIHA cell proliferation and LX-2 cell activation through IL-4 or IL-13. Our data suggest that in HBV-LC patients, highly activated peripheral iNKT cells may migrate to the liver and affect hepatocyte cell line (MIHA) proliferation and hepatic stellate cell line (LX-2) activation through the expression of type 2 cytokines, which may result in excessive healing and contributing to the progression of fibrosis toward cirrhosis in liver.
不变自然杀伤 T(iNKT)细胞表达 T 细胞和自然杀伤细胞的标志物，可能产生各种细胞因子来调节肝脏免疫。然而，iNKT 细胞在乙型肝炎病毒相关肝硬化(HBV-LC)进展中的作用尚不完全清楚。在这里，我们研究了外周 iNKT 细胞对一组 HBV-LC 患者的影响。用流式细胞术检测外周 iNKT 细胞的频率、数量、激活状态、凋亡和增殖能力。用流式细胞术和 PCR 检测外周 iNKT 细胞对肝细胞系(MIHA)增殖和肝星状细胞系(LX-2)激活的影响。在 HBV-LC 患者中，外周 iNKT 细胞的频率和绝对数显著减少，但 CD25、白细胞介素(IL)-4、IL-13 和干扰素(IFN)-γ的表达水平增加。HBV-LC 患者和健康对照者(HCs)之间循环 iNKT 细胞的增殖和凋亡无差异。CXCR6(CD186)，已知与 iNKT 细胞从外周迁移到肝脏密切相关，在 HBV-LC 患者的外周 iNKT 细胞中高度表达。此外，外周 iNKT 细胞通过 IL-4 或 IL-13 对 MIHA 细胞增殖和 LX-2 细胞激活有深远影响。我们的数据表明，在 HBV-LC 患者中，高度激活的外周 iNKT 细胞可能通过表达 2 型细胞因子迁移到肝脏，并影响肝细胞系(MIHA)增殖和肝星状细胞系(LX-2)激活，这可能导致过度愈合，并导致肝脏纤维化向肝硬化进展。
