Integrated analyses reveal CST7 and DUSP5 regulate Th2 cells differentiation to promote chronic HBV infection

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.