Decoding the distinct immune landscape and possible regulatory mechanisms of autoimmune hepatitis through integrated single-cell and bulk RNA sequencing

Abstract

Objectives Autoimmune hepatitis (AIH) is a complex immune-mediated liver disorder characterized by dysregulated immune responses. This study aimed to decode the distinct immune landscape and regulatory mechanisms of AIH using integrated single-cell and bulk RNA sequencing. Methods The data of single-cell RNA-seq (scRNA-seq) and bulk RNA-seq were downloaded from GEO database. The cell clustering, differential gene expression, trajectory analysis, functional enrichment, and cell-cell communication were performed were analyzed using R software. Results Five major immune cell types were identified, with CD8 + T cells and NK cells significantly expanded in AIH. Functional enrichment showed upregulation of immune activation, inflammation, and metabolic pathways in these cells. The cell-cell communication analysis revealed robust interactions between CD8 + T and NK cells, primarily driven by the CCL5-CCR signaling axis. Integrative analysis of scRNA-seq and bulk RNA-seq identified four common DEIRGs (ITK, IL7R, CXCR4 and SORT1) and one transcription factor PRDM1. Conclusion This study identified dysregulated immune cell clusters, signaling pathways, and potential therapeutic targets in AIH.