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Updated: Jun 6, 2025
Induction of Drug-Induced, Autoimmune Hepatitis in BALB/c Mice for the Study of Its Pathogenic Mechanisms
Published on: May 29, 2020
1,25(OH)2D3-treated mouse bone marrow-derived dendritic cells alleviate autoimmune hepatitis in mice by improving
Juan Dai1, Jianguo Song1,2, Xueping Chen3
1Department of Gastroenterology, The First People's Hospital of Changzhou, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China.
Objective:
Autoimmune hepatitis (AIH) is a chronic progressive autoimmune disease with unclear etiology. As a bioactive metabolite of Vitamin D, 1,25(OH)2D3 can stimulate the production of tolerogenic dendritic cells (DCs) that overexpress programmed cell death ligand 1 (PD-L1). Although these cells have been shown to play a part in autoimmune diseases, their role in AIH remains unclear.
Methods:
This study aimed to investigate the potential effect of 1,25(OH)2D3-modulated DCs (PD-L1high VD3-DCs) in a murine model of experimental autoimmune hepatitis (EAH).
Results:
Our results showed that intravenous injection of PD-L1high VD3-DCs significantly attenuated liver injury and EAH severity in mice. In addition, PD-L1high VD3-DC infusion improved the imbalance between splenic regulatory T cells (TFR) and follicular helper T (TFH) cells in EAH mice by increasing the number of TFR cells and restoring TFR/TFH ratio. Also, PD-L1high VD3-DC infusion selectively promoted TFR expansion and inhibited TFH differentiation. Furthermore, PD-L1high VD3-DC infusion increased TGF-β and IL-10 production, inhibited IL-21 secretion, upregulated key TFH transcriptional factors, and reduced the levels of serum immunoglobulins in EAH mice.
Conclusions:
To sum up, PD-L1high VD3-DC infusion could control EAH progression in mice by regulating TFR/TFH imbalance, indicating PD-L1high VD3-DC infusion might be a promising therapeutic approach for AIH treatment.
