Mesenchymal stem cell alleviate concanavalin A-induced hepatitis via immune reprogramming and complement regulation

Area of Science:

• Immunology
• Hepatology
• Stem Cell Biology

Background:

• Concanavalin A (ConA)-induced hepatitis is a model for immune-mediated liver injury.
• Mesenchymal stem cells (MSCs) show potential in mitigating liver injury via immunomodulation.
• The precise mechanisms of MSCs in liver injury remain unclear.

Purpose of the Study:

• To elucidate the role of MSCs in modulating the hepatic immune microenvironment during ConA-induced acute liver injury using single-cell RNA sequencing (scRNA-seq).

Main Methods:

• Isolation of liver cells from ConA-treated mice with or without MSC treatment.
• scRNA-seq library generation and data analysis using Seurat.
• Trajectory analysis with Monocle 3 and cell-cell communication analysis with CellChat.
• In situ validation using multiplex immunohistochemistry (mIHC).

Main Results:

• MSC treatment alleviated ConA-induced liver injury.
• scRNA-seq revealed selective immune compartment remodeling, including reduced MDSCs, Tregs, NK cells, and proliferating CD8+ T cells, with increased monocyte-derived macrophages (MoMFs).
• MoMFs exhibited heterogeneous states and were identified as a signaling hub, with complement-associated signaling influencing MDSCs and NK cells.

Conclusions:

• MSCs ameliorate immune-mediated liver injury through selective immune microenvironment remodeling, particularly affecting MoMFs.
• MSC treatment alters MoMF composition and communication pathways, contributing to injury resolution.
• These findings offer insights into innate immune mechanisms of MSC-mediated hepatoprotection.