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

Mediators Inflamm. 2018 Mar 4:2018:3069521. doi: 10.1155/2018/3069521. eCollection 2018.

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.

MeSH terms

  • Adolescent
  • Adult
  • Cell Polarity / drug effects
  • Diamines / pharmacology
  • Female
  • Flow Cytometry
  • Humans
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism
  • Interleukin-17 / genetics
  • Interleukin-17 / metabolism
  • Male
  • Middle Aged
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
  • Psoriasis / genetics
  • Psoriasis / immunology*
  • Psoriasis / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Receptor, Notch1 / genetics
  • Receptor, Notch1 / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • 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
  • Young Adult

Substances

  • 24-diamino-5-phenylthiazole
  • Diamines
  • Interleukin-17
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Receptor, Notch1
  • Thiazoles
  • Transcription Factor HES-1
  • Interleukin-10