Department of Gastroenterology and Hepatology, Guangzhou Key Laboratory of Digestive Diseases, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China.
Department of Clinical Laboratory, The First People's Hospital of Foshan, Foshan, Guangdong, China.
Genes Immun. 2024 Oct;25(5):423-433. doi: 10.1038/s41435-024-00296-1. Epub 2024 Sep 5.
Chronicity of HBV infection is a complex process influenced by both viral and host factors. Understanding the complex interplay between HBV and cellular immunity is critical. In this study, we used bulk expression datasets for CHB liver tissue from GSE83148 and GSE84044, and scRNA-seq data of CHB liver samples from GSE182159 to find critical genes and immune cells accounted for CHB. We first identified DEGs closely associated with CHB by WGCNA and these genes were intricately linked to differentiation of Th2 cells, which were significantly higher in CHB and positively associated with ALT, AST, HBV-DNA, Scheuer grade and Scheuer stage. Among these DEGs, CST7 and DUSP5 highly expressed in CHB and positively associated with ALT, AST, HBV-DNA, Scheuer grade and Scheuer stage. Moreover, through scRNA-seq, we also found that CST7 and DUSP5 upregulated in Th2 cells and regulated differentiation of naive CD4+ T cells to Th2 cells. Finally, in-vitro studies also showed that HBV infection could significantly up-regulate DUSP5 and CST7 expression. This research strongly revealed that HBV could up-regulate CST7 and DUSP5 to drive differentiation of naive CD4+ T cells into Th2 cells and contribute to CHB, which may pave the way for immunotherapeutic interventions.
HBV 感染的慢性化是一个受病毒和宿主因素共同影响的复杂过程。了解 HBV 与细胞免疫之间的复杂相互作用至关重要。在这项研究中，我们使用了 GSE83148 和 GSE84044 中 CHB 肝组织的批量表达数据集，以及 GSE182159 中 CHB 肝样本的 scRNA-seq 数据，以寻找与 CHB 相关的关键基因和免疫细胞。我们首先通过 WGCNA 鉴定了与 CHB 密切相关的差异表达基因（DEGs），这些基因与 Th2 细胞的分化密切相关，在 CHB 中显著升高，并与 ALT、AST、HBV-DNA、Scheuer 分级和 Scheuer 分期呈正相关。在这些 DEGs 中，CST7 和 DUSP5 在 CHB 中高表达，并与 ALT、AST、HBV-DNA、Scheuer 分级和 Scheuer 分期呈正相关。此外，通过 scRNA-seq，我们还发现 CST7 和 DUSP5 在 Th2 细胞中上调，并调节幼稚 CD4+T 细胞向 Th2 细胞的分化。最后，体外研究也表明 HBV 感染可显著上调 DUSP5 和 CST7 的表达。这项研究强烈表明，HBV 可以上调 CST7 和 DUSP5，从而驱动幼稚 CD4+T 细胞向 Th2 细胞分化，并促进 CHB 的发生，这可能为免疫治疗干预铺平道路。
