Abstract
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.
Highlights
Psoriasis is a CD4+ T cell-medicated autoimmune and inflammatory cutaneous disorder, which affects 2% to 3% of the world population [1]
Th17 cell percentage in peripheral CD4+ T cells was significantly higher in psoriasis vulgaris (PV) patients than healthy controls (3.91 ± 0.76% versus 0.63 ± 0.13%, t = 25 549, P < 0 001, Figure 1(c))
Treg cell percentage was dramatically decreased in PV patients compared with healthy controls (1.90 ± 0.33% versus 4.05 ± 0.64%, t = −17 041, P < 0 001, Figure 1(d))
Summary
Psoriasis is a CD4+ T cell-medicated autoimmune and inflammatory cutaneous disorder, which affects 2% to 3% of the world population [1]. IL-17-expressing T cells (termed Th17) and CD4+CD25+Foxp3+ regulatory T cells (termed Treg) are newly defined CD4+ T cell subsets, which have opposite effects on autoimmunity and inflammation. Th17 cells play a crucial role in the pathogenesis and development of autoimmune and inflammatory reactions by producing high levels of IL-17. Treg cells, characterized by high expression of the transcription factor Foxp, are considered to be important for maintaining self-tolerance and preventing autoimmune and inflammatory diseases by directly contacting effective immune cells; releasing suppressive cytokines, such as IL-10 and transforming growth factor(TGF-) β; and exhibiting their immunosuppressive effects on T cells [4,5,6]. Th17/Treg immune imbalance has been proved to widely exist in autoimmune and inflammatory diseases [7,8,9]. The possible roles of Th17 and Treg cells in the pathogenesis of PV have been reported; the results were not completely consistent [10,11,12,13]
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