Resveratrol Inhibits AhR/Notch Axis and Reverses Th17/Treg Imbalance in Purpura by Activating Foxp3

Overview

Journal Toxicol Res (Camb)

Publisher Oxford University Press

Date 2023 Jul 3

PMID 37397914

Authors

Jing Cheng

Sheng Wang

Shi-Qin Lv

Yuan Song

Ning-Hong Guo

Affiliations

Soon will be listed here.

Abstract

Background: Resveratrol has been reported to reverse the imbalance of T helper 17/regulatory T (Th17/Treg) by inhibiting the aryl hydrocarbon receptor pathway to treat immune thrombocytopenia. However, the regulation mechanism of the Notch signaling pathway by resveratrol has not been reported in purpura. This study is aimed to explore the mechanism of resveratrol ultrafine nanoemulsion (Res-mNE) in immune thrombocytopenia.

Methods: The immune thrombocytopenia mouse model was constructed to explore the effect of RES-mNE on immune thrombocytopenia. Cluster of differentiation 4 (CD4) T cells were isolated and treated with different medications. CD4 T cells were induced to differentiate into Th17 cells and Treg cells. Flow cytometry was used to detect the proportion of Th17 cells and Treg cells. The secretion was measured by the enzyme-linked immunosorbent assay (ELISA). Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and western blot were used to detect the mRNA and protein levels.

Results: Th17 cells, IL-17A and IL-22 increased in the immune thrombocytopenia mouse model, and the Treg cells and IL-10 decreased. Res-mNE promoted Treg cell differentiation and IL-10 secretion in CD4 T cells while inhibiting Th17 cell differentiation and IL-17A and IL-22 levels. The AhR activator 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) reversed the effect of Res-mNE. Notch inhibitors reduced the ratio of Th17/Treg differentiation. Res-mNE activated the expression of Foxp3 by mediating AhR/Notch signaling to reverse the imbalance of Th17/Treg differentiation in immune thrombocytopenia.

Conclusion: Taken together, our findings demonstrated that RES-mNE inhibited the AhR/Notch axis and reversed Th17/Treg imbalance by activating Foxp3.

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