Zhuo Yue, Wu Hongzheng, Zhao Wenying, Yin Sheng, Lei Fang, Pang Xueyang, Sun Wei, Feng Lifeng, Jia Shulei, Li Wanzhen, Li Yang, Ren Jiling, Wang Min, Zhou Dongming
Tianjin Key Laboratory of Pathogenic Microbiology of Infectious Disease, Tianjin Centers for Disease Control and Prevention, Tianjin, China.
Department of Pathogen Biology, Basic Medical College, Tianjin Medical University, Tianjin, China.
Hepatol Commun. 2025 Apr 14;9(5). doi: 10.1097/HC9.0000000000000672. eCollection 2025 May 1.
Chronic hepatitis B (CHB) infection results in persistent liver inflammation, which ultimately leads to liver fibrosis and increases the risk of cirrhosis. Recruitment of circulating monocytes to the liver is an essential aspect that exacerbates liver fibrosis; however, the mechanism underlying their dysregulation, which contributes to this progression, remains unclear.
Single-cell RNA sequencing was performed to characterize the landscape of circulating monocytes from patients with CHB and liver fibrosis (CHB group) and healthy controls (HC group). Conventional techniques were performed to validate the findings.
Monocytes significantly expanded in the CHB group. The proto-oncogene LIM domain only 2 (LMO2) was highly expressed in monocytes from the CHB group, which may be associated with their expansion. In addition, we noticed that a classical monocyte subcluster surged in the CHB group and highly expressed platelet-related genes such as ITGA2B, which was identified as monocyte-platelet aggregates (MPA). The frequency of MPA was significantly higher in the CHB group, positively associated with platelet and white blood cell, and negatively associated with liver fibroscan and age, which indicates that MPA may play an important role in liver inflammation in the early liver fibrosis stage. Moreover, we found that MPA displays the enrichment of chemokine signaling-associated genes, such as C-C chemokine motif ligand 5 (CCL5), and showed an increased adhesion capacity to endothelial cells. After incubation with MPA cell supernatants, pro-inflammatory factors such as IL-8 and IL-1β were upregulated in LX-2 cells, which were reversed by the addition of anti-CCL5 antibodies.
Our data suggest that enhanced LMO2 expression in circulating monocytes may be associated with their expansion, and an increased MPA subset may participate in liver fibrosis progression. These results provide valuable insights into the etiology of liver fibrosis in patients with CHB.
慢性乙型肝炎（CHB）感染会导致持续性肝脏炎症，最终导致肝纤维化并增加肝硬化风险。循环单核细胞向肝脏募集是加剧肝纤维化的一个重要方面；然而，导致这种进展的单核细胞失调的潜在机制仍不清楚。
进行单细胞RNA测序以表征CHB和肝纤维化患者（CHB组）及健康对照（HC组）的循环单核细胞图谱。采用传统技术验证研究结果。
CHB组中单核细胞显著扩增。原癌基因LIM结构域仅2（LMO2）在CHB组的单核细胞中高表达，这可能与其扩增有关。此外，我们注意到CHB组中一个经典单核细胞亚群激增，且高表达血小板相关基因如整合素α2β（ITGA2B），其被鉴定为单核细胞 - 血小板聚集体（MPA）。CHB组中MPA的频率显著更高，与血小板和白细胞呈正相关，与肝脏弹性成像及年龄呈负相关，这表明MPA可能在肝纤维化早期的肝脏炎症中起重要作用。此外，我们发现MPA显示趋化因子信号相关基因如C - C趋化因子基序配体5（CCL5）富集，并表现出对内皮细胞的黏附能力增强。用MPA细胞上清液孵育后，LX - 2细胞中白细胞介素 - 8（IL - 8）和白细胞介素 - 1β等促炎因子上调，而添加抗CCL5抗体可使其逆转。
我们的数据表明，循环单核细胞中LMO2表达增强可能与其扩增有关，而增加的MPA亚群可能参与肝纤维化进展。这些结果为CHB患者肝纤维化的病因提供了有价值的见解。
