Dataset Information

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

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 ROR?t 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.

SUBMITTER: Shi Y

PROVIDER: S-EPMC6693306 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

Shi Yuling Y Chen Zeyu Z Zhao Zihan Z Yu Yingyuan Y Fan Huayu H Xu Xiaoguang X Bu Xiaolin X Gu Jun J

Frontiers in immunology 20190807

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 les ...[more]

PMID: 31440249

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Project description:IntroductionPsoriasis is an immune-mediated, chronic, inflammatory disease, which has a substantial humanistic and economic burden. This study aimed to assess the impact of this disease on health-related quality of life (HRQoL), work productivity, and direct and indirect costs from a societal perspective among Brazilian patients.MethodsThis is a cross-sectional, observational, multicenter study, enrolling patients with moderate to severe plaque psoriasis according to physician evaluation. Data collection was performed from December 2015 to November 2016 through face-to-face interviews using a structured questionnaire and five standardized patient-reported outcomes instruments. Direct costs were estimated by multiplying the amount of resources used (12-month recall period) by the corresponding unit cost. Indirect costs were grouped in two time horizons: annual costs (income reduction and absenteeism) and lifetime costs (demission and early retirement).ResultsA total of 188 patients with moderate to severe plaque psoriasis were included, with mean age of 48.0 (SD 13.1). "Anxiety and depression" and "pain and discomfort" were the most impaired dimensions, according to the EuroQol Five-Dimension-Three-Level (EQ-5D-3L). The highest effect was found for "symptoms and feelings" [mean (SD) 2.4 (1.7)] Dermatology Life Quality Index (DLQI) subscale. Psoriatic arthritis (PsA) presence and biologic-naïve status were associated with worse HRQoL. Presenteeism was more frequent than absenteeism, according to the Work Productivity and Activity Impairment questionnaire-General Health (WPAI-GH) [17.4% vs. 6.3%], while physical demands and time management were the most affected Work Limitations Questionnaire (WLQ) subscales [means (SD) 23.5 (28.5) and 17.7 (24.9), respectively]. The estimated annual cost per patient was USD 4034. Direct medical costs accounted for 87.7% of this estimate, direct non-medical costs for 2.4%, and indirect costs for 9.9%.ConclusionsResults evidenced that moderate to severe plaque psoriasis imposes substantial costs to society. Our data showed that this disease negatively affects both work productivity and HRQoL of Brazilian patients. Subgroups with PsA and biologic-naïve patients presented lower HRQoL, showing the impact of this comorbidity and the relevance of biologics in psoriasis treatment.FundingNovartis Biociências S.A.

Dataset Information

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

Publications

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

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