Medical School, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China.
Department of Gastroenterology Disease, The First People's Hospital of Jintan District, Changzhou, 213200, China.
BMC Infect Dis. 2023 Oct 24;23(1):719. doi: 10.1186/s12879-023-08723-w.
Chronic HBV infection is always accompanied by differences in the balance between regulatory T cells (Tregs) and T-helper 17 (Th17) cells in infection phases. IL-21 plays an important role in the progression of chronic HBV infection. Thus, the aim of our study was to investigate the role of the regulatory function of IL-21 in maintaining the balance between Tregs and Th17 cells in chronic HBV infection.
Twenty-five chronic HBV-infected patients in the immune-tolerant (IT) phase and 23 chronic hepatitis B (CHB) patients were recruited in this study. Cytokines production was measured by ELISA. The mRNA expression levels were determined by qPCR. CD4T cells were stimulated with or without IL-21. Tregs and Th17 cells were measured by flow cytometry. pSTAT3 and STAT3 expression was assessed by Western blotting.
The concentration of IL-21 in the serum of CHB were significantly higher than that in the serum from IT patients, and IL-21 and IL-21R levels in the PBMCs from CHB were higher than those from IT patients. IL-21 promoted Th17 cells differentiation and function but inhibited Treg cells differentiation and function by activating STAT3 signaling pathways, upregulating RORγt expression, downregulating Foxp3 expression, by increasing IL-17and IL-22 secretion, and decreasing TGF-β secretion in chronic HBV infection. The proportion of Tregs and TGF-β concentrations in CHB was significantly lower than that in IT patients. Furthermore, the percentage of Th17 cells and the IL-17 concentration in CHB was markedly higher than that in IT patients, causing a reduction in the Tregs/Th17 ratio in CHB patients.
Our results suggest that IL-21 may contribute to inflammation in chronic HBV infection by modulating the balance between Treg and Th17 cells.
慢性乙型肝炎病毒（HBV）感染始终伴随着感染阶段调节性 T 细胞（Tregs）和辅助性 T 细胞 17（Th17）细胞之间平衡的差异。IL-21 在慢性 HBV 感染的进展中发挥重要作用。因此，本研究旨在探讨 IL-21 的调节功能在维持慢性 HBV 感染中 Tregs 和 Th17 细胞之间平衡中的作用。
本研究纳入了 25 例免疫耐受（IT）期慢性 HBV 感染者和 23 例慢性乙型肝炎（CHB）患者。通过 ELISA 法检测细胞因子的产生，qPCR 法检测 mRNA 表达水平。通过 IL-21 刺激或不刺激 CD4T 细胞，通过流式细胞术检测 Tregs 和 Th17 细胞，通过 Western blot 法检测 pSTAT3 和 STAT3 的表达。
CHB 患者血清中 IL-21 的浓度明显高于 IT 患者，CHB 患者外周血单个核细胞（PBMCs）中的 IL-21 和 IL-21R 水平高于 IT 患者。IL-21 通过激活 STAT3 信号通路，上调 RORγt 表达，下调 Foxp3 表达，增加 IL-17 和 IL-22 的分泌，减少 TGF-β的分泌，促进 Th17 细胞的分化和功能，但抑制 Treg 细胞的分化和功能，在慢性 HBV 感染中。CHB 患者的 Tregs 比例和 TGF-β浓度明显低于 IT 患者。此外，CHB 患者的 Th17 细胞比例和 IL-17 浓度明显高于 IT 患者，导致 CHB 患者的 Tregs/Th17 比值降低。
我们的研究结果表明，IL-21 通过调节 Treg 和 Th17 细胞之间的平衡，可能导致慢性 HBV 感染中的炎症。
