The CNTN1/Gilz pathway mediates the therapeutic effect of mesenchymal stem cells on Echinococcus multilocularis-induced hepatic inflammation and fibrosis.

Mesenchymal stem cells (MSCs) exhibit potent immunomodulatory properties, yet their precise mechanisms in alleviating Echinococcus multilocularis-induced hepatic inflammation and fibrosis in Alveolar Echinococcosis (AE) remain elusive. This study aimed to elucidate the immunoregulatory mechanisms underlying MSCs therapy in AE. Using an AE mouse model, we demonstrated that MSCs administration significantly ameliorated liver histopathology, attenuated fibrosis, and restored liver function. Molecular analyses revealed that AE infection promoted a pro-inflammatory profile (elevated RORγt and IFN-γ) while suppressing regulatory factors (FOXP3, TGF-β1, IL-10, CNTN1, and Gilz), effects that were robustly reversed by MSCs treatment. In vitro, co-culture of CNTN1-knockdown MSCs with E. multilocularis antigen-stimulated CD4+ T cells demonstrated that CNTN1 deficiency impaired MSCs-mediated immunoregulation, decreased IL-10 secretion, and disrupted the Th17/Treg balance. Mechanistically, dual-luciferase reporter assays confirmed that CNTN1 directly activates the Gilz promoter. Collectively, our findings identify the CNTN1/Gilz signaling axis as an essential mediator of MSCs immunomodulation, providing novel mechanistic insights into the therapeutic efficacy of MSCs against E. multilocularis-induced hepatic injury.