Astaxanthin Alleviates Autoimmune Hepatitis by Modulating CD8T Cells: Insights From Mass Cytometry and Single-Cell RNA Sequencing Analyses.

Abstract

Astaxanthin (ASX) is an oxygen-containing non-vitamin A carotenoid pigment. However, the role of ASX in autoimmune hepatitis (AIH) remains unclear. In this study, a mouse model of AIH is established induced by concanavalin A (ConA). Mass cytometry and single-cell RNA sequencing (scRNA-seq) are used to analyze the potential role of ASX in regulating the immune microenvironment of AIH. ASX treatment effectively alleviated liver damage induced by ConA and downregulated pro-inflammatory cytokines production in mice. Mass cytometry and scRNA-seq analyses revealed a significant increase in the number of CD8T cells following ASX treatment. Functional markers of CD8T cells, such as CD69, MHC II, and PD-1, are significantly downregulated. Additionally, specific CD8T cell subclusters (subclusters 4, 13, 24, and 27) are identified, each displaying distinct changes in marker gene expression after ASX treatment. This finding suggests a modulation of CD8T cell function by ASX. Finally, the key transcription factors for four subclusters of CD8T cells are predicted and constructed a cell-to-cell communication network based on receptor-ligand interactions probability. In conclusion, ASX holds the potential to ameliorate liver damage by regulating the number and function of CD8T cells.