Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on NAFLD Diagnosis, Beijing, China.
Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China.
Front Immunol. 2023 Mar 16;14:1127572. doi: 10.3389/fimmu.2023.1127572. eCollection 2023.
The disease burden caused by chronic hepatitis B virus (HBV) infection is still heavy, and the current treatment scheme has not achieved a complete cure. Changes in natural and adaptive immunity usually accompany chronic HBV infection. As a marker expressed on dendritic cells (DCs), whether lysosome-associated membrane glycoprotein 3 (LAMP3) participates in chronic HBV infection deserves further analysis.
We retrieved chronic HBV infection transcriptional information from the Gene Expression Omnibus (GEO) database. The LAMP3 expression in the liver of patients with chronic hepatitis B (CHB) was analyzed in three GEO datasets and confirmed in our validation cohort (27 patients with CHB). Differentially expressed genes were obtained from one CHB cohort by comparing LAMP3 and LAMP3 expression subgroups. These genes underwent Gene Ontology, Kyoto Encyclopedia of Genes and Genomes analysis, and Gene Set Enrichment Analysis to decipher the influence of LAMP3 on the biological process and immunity changes in HBV infection. Furthermore, we investigated the potential relationship between LAMP3 levels, the abundance of infiltrating immune cells, and liver dysfunction.
Compared to healthy controls, LAMP3 expression was upregulated in the transcriptional profiles of the liver in patients with CHB. The high LAMP3 expression was related to T cell activation and the chemokine signaling pathway. The LAMP3 gene was positively linked to marker sets of infiltrating activated regulatory T cells (Treg), T cell exhaustion, monocytes, and DCs. Moreover, CHB patients with high LAMP3 expression had unfavorable liver dysfunction.
LAMP3 is a gene related to HBV infection, which might be involved in HBV infection by regulating T cell activation and adaptive immune response.
慢性乙型肝炎病毒（HBV）感染引起的疾病负担仍然很重，目前的治疗方案尚未实现完全治愈。天然和适应性免疫的变化通常伴随着慢性 HBV 感染。作为树突状细胞（DCs）上表达的标志物，溶酶体相关膜糖蛋白 3（LAMP3）是否参与慢性 HBV 感染值得进一步分析。
我们从基因表达综合数据库（GEO）中检索了慢性 HBV 感染的转录信息。在三个 GEO 数据集和我们的验证队列（27 例慢性乙型肝炎患者）中分析了慢性乙型肝炎患者肝组织中 LAMP3 的表达。通过比较 LAMP3 和 LAMP3 表达亚组，从一个慢性乙型肝炎队列中获得差异表达基因。这些基因进行了基因本体论、京都基因与基因组百科全书分析和基因集富集分析，以破译 LAMP3 对 HBV 感染中生物学过程和免疫变化的影响。此外，我们研究了 LAMP3 水平与浸润免疫细胞丰度和肝功能障碍之间的潜在关系。
与健康对照组相比，慢性乙型肝炎患者肝组织转录谱中 LAMP3 的表达上调。高 LAMP3 表达与 T 细胞激活和趋化因子信号通路有关。LAMP3 基因与浸润性激活调节性 T 细胞（Treg）、T 细胞耗竭、单核细胞和 DCs 的标志物集呈正相关。此外，LAMP3 表达水平高的慢性乙型肝炎患者肝功能不良。
LAMP3 是与 HBV 感染相关的基因，可能通过调节 T 细胞激活和适应性免疫反应参与 HBV 感染。
