Xu Chuanlu, Su Yao, Lu Wenjing, Dong Jiaqi, Wang Luyao, Mi Yabing, Jia Xinrui, Lv Wenqi, Wu Shengyu, Jia Yuanhui, Ying Hao
Department of Obstetrics, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, China.
Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, China.
Virol J. 2025 Jul 18;22(1):245. doi: 10.1186/s12985-025-02879-4.
Postpartum hepatitis flares have been commonly described, but the specific mechanism is unclear.
Our objective was to explore estrogen's role in postpartum hepatitis flares in HBV transgenic mice.
The numbers of intrahepatic CD4CD25Foxp3 regulatory T cells (Tregs) and the levels of the inhibitory cytokine IL-10 were determined in concanavalin A (Con A)-injected mice with and without estrogen injection postpartum. The role of intrahepatic CD4CD25Foxp3Tregs in suppressing immune responses was investigated by systemically depleting intrahepatic CD25 cells in mice treated with an anti-CD25 mAb. We employed the PI3K inhibitor LY294002 to investigate the function of the PI3K/Akt pathway in regulating the suppressive activity of intrahepatic CD4CD25Foxp3Tregs in vivo.
A higher percentage of CD4CD25Foxp3Tregs accumulated in the liver with increasing physiological E2 levels during pregnancy, declined sharply by day 7 postpartum. We discovered that estrogen regulates the proliferation and activation of intrahepatic CD4CD25Foxp3 Tregs via the PI3K/Akt signaling cascade and participates in hepatitis immune regulation. Furthermore, E2 administration postpartum increased intrahepatic CD4CD25Foxp3Tregs and inhibitory cytokine IL-10, which inhibit the immune clearance of CD8 T cells and NK cells along with decreased cytotoxic cytokine IFN-γ and TNF-α levels.
Estrogen protects against postpartum Con A-induced hepatitis by promoting intrahepatic CD4⁺CD25⁺ Treg expansion through activation of the PI3K/Akt signaling pathway in HBV-Tg mice.
产后肝炎发作已被普遍描述，但具体机制尚不清楚。
我们的目的是探讨雌激素在乙肝病毒转基因小鼠产后肝炎发作中的作用。
在产后注射或未注射雌激素的伴刀豆球蛋白A（Con A）注射小鼠中，测定肝内CD4CD25Foxp3调节性T细胞（Tregs）数量和抑制性细胞因子白细胞介素-10水平。通过用抗CD25单克隆抗体处理小鼠全身清除肝内CD25细胞，研究肝内CD4CD25Foxp3Tregs在抑制免疫反应中的作用。我们使用PI3K抑制剂LY294002研究PI3K/Akt途径在体内调节肝内CD4CD25Foxp3Tregs抑制活性中的功能。
随着孕期生理性雌激素水平升高，肝内积累的CD4CD25Foxp3Tregs百分比更高，产后第7天急剧下降。我们发现雌激素通过PI3K/Akt信号级联调节肝内CD4CD25Foxp3 Tregs增殖和活化，并参与肝炎免疫调节。此外，产后给予雌激素增加了肝内CD4CD25Foxp3Tregs和抑制性细胞因子白细胞介素-10，它们抑制CD8 T细胞和NK细胞的免疫清除，同时降低细胞毒性细胞因子干扰素-γ和肿瘤坏死因子-α水平。
在乙肝病毒转基因小鼠中，雌激素通过激活PI3K/Akt信号通路促进肝内CD4⁺CD25⁺ Treg扩增，从而预防产后Con A诱导的肝炎。
