IL-21 Induces an Imbalance of Th17/Treg Cells in Moderate-to-Severe Plaque Psoriasis Patients

Yuling Shi,Huayu Fan,Zihan Zhao,Xiaolin Bu,Xiaoguang Xu,Zeyu Chen,Yingyuan Yu,Jun Gu

doi:10.3389/fimmu.2019.01865

Abstract

Background: Psoriasis is a chronic immune-mediated inflammatory skin disease, with over-activated interleukin (IL)-17-producing CD4+ T cells (Th17) and repressed regulatory T (Treg) cells. IL-21 is a Th17-related cytokine and plays an important role in the pathogenesis of psoriasis. However, the mechanism by which IL-21 affects the pathogenic progress of psoriasis remains poorly understood.Methods: IL-21 and IL-21 receptor (IL-21R) expression in normal and psoriatic lesional skin were determined by immumohistochemical staining, immunofluorescence staining, and western blotting. The levels of IL-21, IL-17A, and IL-22 in the culture supernatants were measured by enzyme-linked immunosorbent assay (ELISA). The level of IL-10 in the culture supernatants was measured by cytometric bead array (CBA). The mRNA expression levels were assessed by quantitative polymerase chain reaction (qPCR). CD4+ T cells were isolated from the peripheral blood mononuclear cells (PBMCs) from the psoriasis patients and healthy individuals and then treated with or without IL-21 for 3 days. The proportions of Th17 and Treg cells were determined by flow cytometric analysis.Results: IL-21 and IL-21R were highly expressed in the lesional skin and peripheral blood of psoriasis patients. IL-21 promoted CD4+ T cells proliferation and Th17 cells differentiation and inhibiting Treg cells differentiation by upregulating RORγt expression and downregulating Foxp3 expression, with increased expression and secretion of IL-17A and IL-22. The proportion of Treg cells was negatively correlated with that of Th17 cells in psoriasis patients.Conclusion: Our results suggest that IL-21 may promote psoriatic inflammation by inducing imbalance in Th17 and Treg cell populations.

Highlights

Psoriasis is a chronic inflammatory skin disease that affects ∼2 and 0.47% of the population in Europe and North America [1] and China [2], respectively
Consistent with the previous studies [26,27,28], we found that the mRNA level of IL-21 and its receptor was higher in the lesional skin of psoriasis patients compared with the skin of healthy individuals (Figure 1A)
The mRNA levels of IL-17A, IL-22, IL-23, RORγt, and IFN-γ were increased in the lesional skin of psoriasis patients (Figure 1B), whereas Foxp3, a vital transcriptional factor of Treg cells, was decreased in psoriasis patients (Figure 1B)

Summary

Introduction

Psoriasis is a chronic inflammatory skin disease that affects ∼2 and 0.47% of the population in Europe and North America [1] and China [2], respectively. Because of genetic and environmental factors, the communication between keratinocytes and immune cells, including T cells, dendritic cells, macrophages, and neutrophils, is impaired in psoriasis [3]. The accumulation of immune cells in the psoriatic lesional skin, such as Th17 cells, can produce abundant inflammatory mediators, such as IL-17A, that lead to the accumulation of neutrophils and impaired differentiation and hyperproliferation of keratinocytes, resulting in epidermal hyperplasia [3]. Psoriasis is a chronic immune-mediated inflammatory skin disease, with over-activated interleukin (IL)-17-producing CD4+ T cells (Th17) and repressed regulatory T (Treg) cells. The mechanism by which IL-21 affects the pathogenic progress of psoriasis remains poorly understood

Methods

Results

Conclusion