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

Abstract

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. 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. 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. This study identified dysregulated immune cell clusters, signaling pathways, and potential therapeutic targets in AIH.