International Archives of Allergy and Immunology

Clinical Allergology - Original Paper

Correlation of PD-1/PD-L1 Signaling Pathway with Treg/Th17 Imbalance from Asthmatic Children

Xi X.a · Liu J.-M.b · Guo J.-Y.a

Author affiliations

aDepartment of Paediatrics, Dongying People’s Hospital, Dongying, China
bDepartment of Clinical Laboratory, Dongying People’s Hospital, Dongying, China

Keywords: AsthmaPD-1/PD-L1 pathwayTreg cellsTh17 cellsImmune imbalance

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Int Arch Allergy Immunol 2018;176:255–267
https://doi.org/10.1159/000489338

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Article / Publication Details

First-Page Preview
Abstract of Clinical Allergology - Original Paper

Received: July 17, 2017
Accepted: April 17, 2018
Published online: June 06, 2018
Issue release date: July 2018

Number of Print Pages: 13
Number of Figures: 7
Number of Tables: 2

ISSN: 1018-2438 (Print)
eISSN: 1423-0097 (Online)

For additional information: https://www.karger.com/IAA

Abstract

Background: The balance between T helper 17 (Th17) and regulatory T cells (Treg) is a new paradigm in asthma pathogenesis, but no therapeutic targets could modulate the Th17/Treg balance specifically for asthma. Since previous studies have shown the programmed cell death-1(PD-1)/PD-ligand 1 (PD-L1) pathway is critical to immune homeostasis in this disease, we hypothesized that the PD-1/PD-L1 pathway might be involved in the regulation of Treg/Th17 imbalance in asthmatic children. Methods: The percentage of Treg and Th17 cells and the expression of PD-1 and PD-L1 were detected by flow cytometry in children with asthma and healthy controls. CD4+ T cells were stimulated with Th17 and Treg differentiating factors, and treated with anti-PD-1. Then cells were harvested and measured for Th17 and Treg percentages and Foxp3 and RORγt levels using RT-PCR. Results: We observed an inverse correlation between the percentages of Treg and Th17 cells, and the expression of PD-1 and PD-L1 in the two subsets also changed in the mild persistent and moderate to severe persistent groups compared with healthy controls. In vitro, administration of anti-PD-1 could decrease Th17 percentages and RORγt mRNA, and increase Treg percentages and Foxp3 mRNA in CD4+ T cells of children with asthma in the mild persistent and moderate to persistent groups. Additionally, the role played by anti-PD-1 in regulating Treg/Th17 balance was further confirmed in an asthmatic mouse model. Conclusion: Alteration of the PD-1/PD-L1 pathway can modulate Treg/Th17 balance in asthmatic children. Treatment with anti-PD-1 posed protective effects on asthma models, providing a novel theoretical target for asthma.

© 2018 S. Karger AG, Basel



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Article / Publication Details

First-Page Preview
Abstract of Clinical Allergology - Original Paper

Received: July 17, 2017
Accepted: April 17, 2018
Published online: June 06, 2018
Issue release date: July 2018

Number of Print Pages: 13
Number of Figures: 7
Number of Tables: 2

ISSN: 1018-2438 (Print)
eISSN: 1423-0097 (Online)

For additional information: https://www.karger.com/IAA

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2018, Vol.176, No. 3-4

July 2018

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Edited by: E. Padovan, Basel. X.X. and J.-M.L. contributed equally to this work.

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