Notch1 Signaling Regulates the Th17/Treg Immune Imbalance in Patients with Psoriasis Vulgaris

• Published in: Mediators of inflammation 2018-01, Vol.2018 (2018), p.1-10
• Main Authors: Gao, MeiLan, Gao, Tianqin, Xue, Haibo, Ma, Lei, Zhang, YuJie
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Care and treatment; CD4 antigen; Cell Polarity - drug effects; Cytokines; Diamines - pharmacology; Disease; Enzyme-linked immunosorbent assay; Female; Flow Cytometry; Foxp3 protein; Gene expression; Helper cells; Humans; Immunology; Inflammatory diseases; Interleukin 10; Interleukin 17; Interleukin-10 - genetics; Interleukin-10 - metabolism; Interleukin-17 - genetics; Interleukin-17 - metabolism; Ligands; Lymphocytes; Lymphocytes T; Male; Middle Aged; Notch1 protein; Nuclear Receptor Subfamily 1, Group F, Member 3 - genetics; Nuclear Receptor Subfamily 1, Group F, Member 3 - metabolism; Pathogenesis; Patients; Polymerase chain reaction; Psoriasis; Psoriasis - genetics; Psoriasis - immunology; Psoriasis - metabolism; Psoriasis vulgaris; Real-Time Polymerase Chain Reaction; Receptor, Notch1 - genetics; Receptor, Notch1 - metabolism; RNA; Secretase; Signal Transduction - drug effects; Signal Transduction - genetics; T cells; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - metabolism; Th17 Cells - drug effects; Th17 Cells - metabolism; Thiazoles - pharmacology; Transcription Factor HES-1 - genetics; Transcription Factor HES-1 - metabolism; Transcription factors; Young Adult
• ISSN: 0962-9351; 1466-1861
• DOI: 10.1155/2018/3069521

Purpose. To evaluate the regulating effect of Notch1 signaling on Th17/Treg immune imbalance in psoriasis vulgaris (PV). Materials and Methods. Notch1, Hes-1, RORγt, Foxp3, IL-17, and IL-10 mRNA expression, as well as Th17 and Treg cell percentages in peripheral CD4+ T cells, were detected by real-time quantitative RT-PCR and flow cytometry, and serum concentrations of IL-17 and IL-10 were detected by ELISA in 36 PV patients and 32 healthy controls. Additionally, CD4+ T cells from 12 PV patients were treated with γ-secretase inhibitor DAPT, and the above indexes were measured. Results. PV patients presented distinct Th17/Treg immune imbalance and highly expressed Notch1 and Hes-1 mRNA levels, which were positively correlated with psoriasis area and severity index (PASI) and the ratios of Th17/Treg and RORγt/Foxp3. DAPT treatment resulted in the obvious downregulation of Th17 cell percentage in cocultured CD4+ T cells, RORγt and IL-17 mRNA levels, and IL-17 concentration in cell-free supernatant from cocultured CD4+ T cells of PV patients in a dose-dependent manner, while there was no significant influence on Treg cell percentage, Foxp3, and IL-10 expression, therefore leading to the recovery of Th17/Treg immune imbalance. Conclusion. Notch1 signaling may contribute to the pathogenesis of PV by regulating Th17/Treg immune imbalance.