华中科技大学张智红研究团队近日取得一项新成果。经过不懈努力，他们报道了神经保护肝门静脉区巨噬细胞减轻肝脏炎症。2025年6月19日出版的《自然—免疫学》发表了这项成果。

通过整合肝脏CX3CR1⁺细胞的全肝叶成像和单细胞RNA测序分析，研究小组发现了CX3CR1⁺CD63⁺肝门区巨噬细胞（LPAMs）的密集网络，与CX3CR1⁺CD207⁺肝包膜巨噬细胞相比，它们表现出转录和空间差异。LPAMs的存活依赖于集落刺激因子1受体（CSF1R）。LPAMs在出生后定植在小鼠的肝门静脉区，并在肝脏稳态期间从骨髓来源的细胞中补充。LPAMs有效地捕获来自肝细胞的抗原，并与门静脉周围的交感神经密切相互作用。肝性非酒精性脂肪性肝炎中LPAMs的缺失导致中性粒细胞浸润增加和交感神经变性恶化。总之，他们的结果提供了对维持肝脏免疫稳态的神经相关门脉巨噬细胞的独特亚群的见解。

研究人员表示，组织巨噬细胞在维持肝脏稳态中具有重要作用，其功能与空间定位密切相关。

附：英文原文

Title: Neuroprotective liver portal area macrophages attenuate hepatic inflammation

Author: Xu, Mengli, Liu, Zheng, Pan, Qi, Cai, Zhenzhen, Li, Xinlin, Huang, Songlin, Wang, Xinru, Xu, Yilun, Liu, Jiayang, Zhai, Yujie, Yang, Jie, Li, Borui, Fan, Zhan, Lu, Yafang, Gao, Lulu, Han, Yutong, Luo, Qingming, Zhang, Zhihong

Issue&Volume: 2025-06-19

Abstract: Tissue macrophages have an important role in the maintenance of liver homeostasis, and their functions are closely related to spatial localization. Here, through integration of whole liver lobe imaging and single-cell RNA sequencing analysis of CX3CR1+ cells in the mouse liver, we identified a dense network of CX3CR1+CD63+ liver portal area macrophages (LPAMs) that exhibited transcriptional and spatial differences compared with CX3CR1+CD207+ liver capsular macrophages. The survival of LPAMs was dependent on colony-stimulating factor 1 receptor (CSF1R). LPAMs colonized the hepatic portal area of mice after birth and were replenished from bone-marrow-derived cells during liver homeostasis. LPAMs efficiently captured antigens derived from hepatocytes and closely interacted with sympathetic nerves around the portal vein. Deletion of LPAMs led to increased neutrophil infiltration and worsened sympathetic nerve degeneration during hepatic nonalcoholic steatohepatitis. In summary, our results provide insights into a distinct subset of nerve-associated portal macrophages that function to maintain liver immune homeostasis.

DOI: 10.1038/s41590-025-02190-y

Source: https://www.nature.com/articles/s41590-025-02190-y