Immunopharmacology and immunotoxicology · 2024
1,25(OH)2D3-treated mouse bone marrow-derived dendritic cells alleviate autoimmune hepatitis in mice by improving TFR/TFH imbalance.
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Dai Juan, Song Jianguo, Chen Xueping, Ding Fei, Ding Yanbo, Ma Liang, Zhang Liwen
Аннотация
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.
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.