Natural Compound 2,2′,4′-Trihydroxychalcone Suppresses T Helper 17 Cell Differentiation and Disease Progression by Inhibiting Retinoid-Related Orphan Receptor Gamma T
Abstract
:1. Introduction
2. Results
2.1. Structure-Based Virtual Screening of Small Molecules Targeting RORγt
2.2. TDC Suppressed RORγt Transcription Activity In Vitro
2.3. TDC Inhibited Th17 Cell Differentiation In Vitro
2.4. TDC Efficiently Ameliorated the Onset of EAE and Reduced CNS Inflammation
2.5. TDC Treatment Blocked the Activation of Debdritic Cells (DCs) and MOG-Reactive T Cells in the CNS
2.6. TDC Alleviated DSS-Induced Colitis
2.7. TDC Treatment Decreased the Secretion of Pro-Inflammatory Cytokines and Preserved the Proportion of Th17/Treg Cells
2.8. TDC Alleviated the Transplantation Rejection Responses of Skin Graft In Vivo
2.9. TDC Inhibited Skin Graft Rejection in Allogeneic Mice by Maintaining a Balance between Th17 Cells and Treg Cells
3. Discussion
4. Material and Methods
4.1. Virtual Screening and Molecular Docking
4.2. Luciferase Reporter Assays
4.3. EAE Induction and Treatment
4.4. DSS-Induced Colitis
4.5. Skin Grafting
4.6. Histopathological Analysis
4.7. Th17 Cell Polarization
4.8. Cytokine Measurement by Flow Cytometry and ELISA
4.9. Real-Time Quantitative PCR
4.10. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Conflicts of Interest
Ethics Approval
Abbreviations
References
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Yang, Y.; Qi, W.; Zhang, Y.; Wang, R.; Bao, M.; Tian, M.; Li, X.; Zhang, Y. Natural Compound 2,2′,4′-Trihydroxychalcone Suppresses T Helper 17 Cell Differentiation and Disease Progression by Inhibiting Retinoid-Related Orphan Receptor Gamma T. Int. J. Mol. Sci. 2022, 23, 14547. https://doi.org/10.3390/ijms232314547
Yang Y, Qi W, Zhang Y, Wang R, Bao M, Tian M, Li X, Zhang Y. Natural Compound 2,2′,4′-Trihydroxychalcone Suppresses T Helper 17 Cell Differentiation and Disease Progression by Inhibiting Retinoid-Related Orphan Receptor Gamma T. International Journal of Molecular Sciences. 2022; 23(23):14547. https://doi.org/10.3390/ijms232314547
Chicago/Turabian StyleYang, Yana, Wenhui Qi, Yanyan Zhang, Ruining Wang, Mingyue Bao, Mengyuan Tian, Xing Li, and Yuan Zhang. 2022. "Natural Compound 2,2′,4′-Trihydroxychalcone Suppresses T Helper 17 Cell Differentiation and Disease Progression by Inhibiting Retinoid-Related Orphan Receptor Gamma T" International Journal of Molecular Sciences 23, no. 23: 14547. https://doi.org/10.3390/ijms232314547