The positive feedback loop of furin and TGFβ1 enhances the immune responses of Tregs to hepatocellular carcinoma cells and hepatitis B virus in vitro
The positive feedback loop of furin and TGFβ1 enhances the immune responses of Tregs to hepatocellular carcinoma cells and hepatitis B virus in vitro
复制标题
弗林蛋白酶和TGFβ1的正反馈环在体外增强Tregs对肝细胞癌细胞和乙型肝炎病毒的免疫反应
DOI：
10.1002/cbin.11806
复制
发表时间：
2022-03
影响因子：
3.9
通讯作者：
Yinjie Meng
中科院分区：
文献类型：
--
作者：
Hua Qiu;Na Wang;Dongyi Lin;Ying Yuan;Jinyuan Li;Dewen Mao;Yinjie Meng
翻译后摘要：调节性T细胞（T细胞）可以发挥免疫抑制活性。弗林蛋白酶可以调节调节性T细胞功能、B型肝炎病毒（HBV）持续感染和肝细胞癌（HCC）的发展。然而，弗林蛋白酶是否能够调节TGFAP对HBV和HCC细胞的免疫应答仍然是未知的。本研究建立了HBV 1. 3 P-HepG 2. 3 P-HepG 2细胞与转染过表达furin或敲低furin/转化生长因子β1（TGFβ1）慢病毒颗粒的Treg细胞共培养体系，以研究furin与TGFβ1之间的调控关系以及furin/TGFβ1对Treg活性的影响。此外，在Teff/CTL、Treg和HBV 1. 3 P-HepG 2细胞的共培养系统中探索了Treg中弗林蛋白酶过表达或弗林蛋白酶/TGFβ1敲低对效应T细胞（Teff）/细胞毒性T淋巴细胞（CTL）免疫活性和HBV复制/表达的影响。我们的研究结果表明，在THBV 1. 3 P-HepG 2细胞共培养体系中，THBV 1. 3 P-HepG 2细胞中弗林蛋白酶的表达和TGF β1的分泌显著增加，弗林蛋白酶和TGFβ1形成了一个正反馈环，从而激活了THBV 1. 3 P-HepG 2细胞。在Teff、Treg和HBV 1. 3 P-HepG 2细胞的共培养系统中，Teff中的Furin或TGFβ1敲低促进Teff细胞增殖，刺激白细胞介素-2和干扰素-γ分泌，并抑制HBV复制/基因表达。此外，Furin和TGFβ1的缺失增强了CTL对HBV 1. 3 P-HepG 2细胞的杀伤活性，并抑制了TCLs、CTL和HBV 1. 3 P-HepG 2细胞共培养体系中HBV的复制/基因表达，表明Furin和TGFβ1的正反馈环增强了TCLs对肝癌细胞和HBV的体外免疫应答。
Abstract：Regulatory T cells (Tregs) can exert immunosuppressive activity. Furin can regulate.Treg functions, hepatitis B virus (HBV) persistent infection, and hepatocellular carcinoma (HCC) development. However, it remains unknown whether furin can regulate the immune responses of Tregs to HBV and HCC cells. Here, coculture systems of HBV1.3P‐HepG2.3P‐HepG2 cells and Tregs transduced with or without lentiviral particles that could overexpress furin or knockdown furin/transforming growth factor β1 (TGFβ1) were established to investigate the regulatory relationship between furin and TGFβ1 and the effect of furin/TGFβ1 on Treg activity. Also, the.effects of furin overexpression or furin/TGFβ1 knockdown in Tregs on the immunological activity of effector T cells (Teffs)/cytotoxic T lymphocytes (CTLs) and HBV replication/expression were explored in the coculture system of Teff/CTL,Treg, and HBV1.3P‐HepG2 cells. Our results showed that furin expression and TGFβ1 secretion were notably increased in Tregs, and Furin and TGFβ1 formed a positive feedback loop to activate Tregs in the coculture system of Tregs and HBV1.3P‐HepG2 cells. Furin or TGFβ1 knockdown in Tregs promoted Teff cell proliferation, stimulated interleukin‐2 and interferon‐γ secretion, and inhibited HBV replication/gene expression in the coculture system of Teff, Treg, and HBV1.3P‐HepG2 cells. Moreover, furin or TGFβ1 depletion in Tregs enhanced the killing activity of CTLs against HBV1.3P‐HepG2 cells and curbed HBV replication/gene expression in the coculture system of Tregs, CTLs, and HBV1.3P‐HepG2 cells.In conclusion, the positive feedback loop of furin and TGFβ1 enhanced the immune responses of Tregs to HCC cells and HBV in vitro.
登录
查看更多内容
影响因子：
3.7
作者：
Huang YH;Lin KH;Liao CH;Lai MW;Tseng YH;Yeh CT
通讯作者：
Yeh CT
影响因子：
5.6
作者：
F. Blanchette;P. Rudd;F. Grondin;L. Attisano;C. Dubois
通讯作者：
F. Blanchette;P. Rudd;F. Grondin;L. Attisano;C. Dubois
影响因子：
--
作者：
Declercq J;Brouwers B;Pruniau VP;Stijnen P;Tuand K;Meulemans S;Prat A;Seidah NG;Khatib AM;Creemers JW
通讯作者：
Creemers JW
影响因子：
4.8
作者：
DUBOIS, CM;LAPRISE, MH;LEDUC, R
通讯作者：
LEDUC, R
影响因子：
1.2
作者：
Koziel Mj
通讯作者：
Koziel Mj