Yurong Ju, Lisha Li, Ye Zhao, Zhifeng Yang, Ziheng Zhao, Zhaofei Wu, Xuewen Pang, Wei Wang
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引用次数: 0
Abstract
Background: Allergic rhinitis (AR) represents a significant global health concern that can give rise to numerous diseases and result in labor productivity. T regulatory (Treg) cells are pivotal players in the pathogenesis of AR, and their deficiencies are closely related to Prostaglandin E2 (PGE2). However, the downstream mechanisms of this relationship remain poorly understood.
Objective: This study aims to investigate the inhibitory mechanisms through which PGE2 impacts the differentiation of Treg cells.
Methods: We compared the differentiation of Treg cells from naïve CD4+ T cells of AR patients and healthy controls, with or without the presence of PGE2 by flow cytometry. Intracellular cAMP concentration, mRNA and protein levels of cyclic-AMP dependent protein kinase A (PKA), as well as their downstream target, Peroxisome Proliferator-Activated Receptor-γ (PPAR-γ) were examined in Treg cells from AR and healthy donors. AR mouse model was established by pollen administration.
Results: PGE2 suppressed the differentiation of Treg cells from human naïve CD4+ T cells through the EP4 receptor. Furthermore, in AR patients and AR mouse, the expression of EP4 receptor were observed enhanced. The PGE2-EP4 signal was carried out by activating cAMP-PKA signaling pathway. Subsequently, phospholated PKA would suppress PPAR-γ expression. Treatment of Pioglitazone, a PPAR-γ agonist, was demonstrated to rescue the differentiation of Treg and help alleviate inflammation in the AR mouse model.
Conclusion: In AR disease, the PGE2-EP4 signaling exerts an inhibitory effect on Treg differentiation by influencing the cAMP-PKA pathway and its downstream target PPAR-γ.
期刊介绍：
The Asian Pacific Journal of Allergy and Immunology (APJAI) is an online open access journal with the recent impact factor (2018) 1.747
APJAI published 4 times per annum (March, June, September, December). Four issues constitute one volume.
APJAI publishes original research articles of basic science, clinical science and reviews on various aspects of allergy and immunology. This journal is an official journal of and published by the Allergy, Asthma and Immunology Association, Thailand.
The scopes include mechanism, pathogenesis, host-pathogen interaction, host-environment interaction, allergic diseases, immune-mediated diseases, epidemiology, diagnosis, treatment and prevention, immunotherapy, and vaccine. All papers are published in English and are refereed to international standards.
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