广州医科大学张玉霞课题组宣布他们研究出hepcidin-iron轴失调损害新生儿抗病毒免疫并诱导致死性肝脏病理。2025年12月8日出版的《免疫学》发表了这项成果。

在感染RV的新生小鼠和胆道闭锁（BA）的婴儿中，课题组人员发现持续性I型干扰素（IFN-I）信号传导上调肝细胞和TREM2⁺巨噬细胞中hepcidin的表达。这损害了slc40a1介导的铁排泄，导致脂质过氧化和铁中毒介导的组织损伤。在骨髓细胞中缺乏Slc40a1的小鼠中，铁积累促进了库普弗细胞中的RV复制和IFN-I激活。阻断IFN-I-hepcidin信号传导和铁螯合可减少RV诱导的小鼠组织损伤。在小鼠中，叶酸抑制IFN-I-hepcidin-iron信号传导，在一项开放标签临床试验中，BA婴儿补充叶酸可降低胆管炎和肝移植率。他们的数据表明，hepcidin-iron失调在新生儿RV感染中起着关键作用，并揭示了BA和其他RV相关新生儿疾病的治疗靶点。该临床试验已在中国临床试验注册中心ChiCTR2100050992注册。

据悉，系统性轮状病毒（RV）感染对新生儿的健康构成重大挑战，但潜在的发病机制仍不清楚。

附：英文原文

Title: A dysregulated hepcidin-iron axis impairs antiviral immunity and induces lethal liver pathology in neonates

Author: Yanhui Xu, Xixi Chen, Rongli Fang, Xiaolei Wang, Yanfang Zhang, Huifang Ren, Yunnan Xiao, Yu Ning, Xiaotian Li, Chengwei Chai, Wen Lei, Kanghua Zhong, Jiankun Liang, Qifeng Liang, Yuanyuan Luo, Qiuming He, Zefeng Lin, Zhenhua Luo, Ming Liu, Weiwei Liang, Tingting Chen, Xiaoqiong Gu, Jinbao Liu, Junqiang Lv, Zhi Yao, Hai-Biao Gong, Wan-Yang Sun, Rong-Rong He, Andrew M. Lew, Huimin Xia, Yuzhang Wu, Wenhao Zhou, Zhe Wen, Zhanghua Chen, Yuxia Zhang

Issue&Volume: 2025-12-08

Abstract: Systemic rotavirus (RV) infection poses a substantial health challenge in neonates, but the underlying pathogenesis remains elusive. In RV-infected neonatal mice and infants with biliary atresia (BA), we discovered that persistent type I interferon (IFN-I) signaling upregulated hepcidin expression in hepatocytes and TREM2+ macrophages. This impaired SLC40A1-mediated iron excretion, leading to lipid peroxidation- and ferroptosis-mediated tissue damage. In mice deficient in Slc40a1 in myeloid cells, iron accumulation promoted RV replication and IFN-I activation in Kupffer cells. Blocking IFN-I-hepcidin signaling and iron chelation reduced RV-induced tissue damage in mice. Folic acid suppressed IFN-I-hepcidin-iron signaling in mice, and in an open-label clinical trial, folic acid supplementation in infants with BA reduced cholangitis and liver transplantation rates. Our data show that hepcidin-iron dysregulation plays a critical role in neonatal RV infection and reveal therapeutic targets for BA and other RV-related neonatal diseases. The clinical trial was registered in the Chinese Clinical Trial Registry ChiCTR2100050992.

DOI: 10.1016/j.immuni.2025.11.001

Source: https://www.cell.com/immunity/abstract/S1074-7613(25)00503-5