Hang Le Thi Thuy, Trinh Hoang Kim Tu, An Luong Bac, Tuyet Nguyen Thi, Tho Phan Vinh, Huy Nguyen Tien, Hoa Pham Thi Le
Department of Infectious Diseases, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam.
Center for Molecular Biomedicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam.
Viral Immunol. 2023 Mar;36(2):127-135. doi: 10.1089/vim.2022.0140. Epub 2023 Mar 1.
The regulatory T (Treg) and T helper 17 (Th17) cells modulate the immune response in chronic hepatitis B virus (HBV) infection by promoting immune tolerance and restricting liver damage or stimulating inflammatory response and rendering hepatocyte injury. These cells act through signaling transcription factors and secreting cytokines. We aimed to observe the percentages of Treg, Th17 cells, and their messenger RNA (mRNA) level of forkhead box protein 3 (Foxp3) and retinoid orphan receptor γt (RORγt) in the chronic hepatitis B (CHB)-infected group and CHB patients with hepatitis flare (HF). We recruited 103 participants, including 88 CHB-infected cases and 15 healthy controls (HCs) in Ho Chi Minh City. CHB cases were enrolled into two groups: HBeAg+ CHB infection (e+CHBI; = 42) and HF (including 20 mild HF and 26 severe HF [sHF]). The Foxp3(+)Treg and Th17 cells were measured by flow cytometry. The mRNA levels of Foxp3 and RORγt were analyzed by real-time polymerase chain reaction. The percentages of Foxp3(+)Treg, of Th17, and the Foxp3(+)Treg/Th17 ratio were significantly higher in the sHF compared to the e+CHBI group. The sHF and e+CHBI groups had significantly higher mRNA levels of Foxp3 and RORγt compared to the HC group. Furthermore, a special subset, interleukin 17A(+)Foxp3(+)Treg cells, were observed with a significantly higher percentage in the sHF compared to the e+CHBI group. This finding revealed the contributions of this new subset on the severe flare cases. Our results explained the diversity of T cells and their subsets in the immune response in CHB. This subset should be further investigated as a specific tool in HBV immune response.
调节性T（Treg）细胞和辅助性T细胞17（Th17）通过促进免疫耐受和限制肝损伤，或刺激炎症反应并导致肝细胞损伤，来调节慢性乙型肝炎病毒（HBV）感染中的免疫反应。这些细胞通过信号转录因子和分泌细胞因子发挥作用。我们旨在观察慢性乙型肝炎（CHB）感染组和乙型肝炎发作（HF）的CHB患者中Treg、Th17细胞的百分比，以及叉头框蛋白3（Foxp3）和视黄酸孤儿受体γt（RORγt）的信使核糖核酸（mRNA）水平。我们招募了103名参与者，包括胡志明市的88例CHB感染病例和15名健康对照（HC）。CHB病例分为两组：HBeAg阳性CHB感染（e+CHBI；n = 42）和HF（包括20例轻度HF和26例重度HF [sHF]）。通过流式细胞术检测Foxp3(+)Treg和Th17细胞。通过实时聚合酶链反应分析Foxp3和RORγt的mRNA水平。与e+CHBI组相比，sHF组中Foxp3(+)Treg、Th17的百分比以及Foxp3(+)Treg/Th17比值显著更高。与HC组相比，sHF组和e+CHBI组中Foxp3和RORγt的mRNA水平显著更高。此外，还观察到一个特殊亚群，即白细胞介素17A(+)Foxp3(+)Treg细胞，与e+CHBI组相比，sHF组中该亚群的百分比显著更高。这一发现揭示了这个新亚群在重度发作病例中的作用。我们的结果解释了CHB免疫反应中T细胞及其亚群的多样性。这个亚群应作为HBV免疫反应中的一种特定工具进一步研究。
