Yurong Ju, Lisha Li, Ye Zhao, Zhifeng Yang, Ziheng Zhao, Zhaofei Wu, Xuewen Pang, Wei Wang
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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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":8552,"journal":{"name":"Asian Pacific journal of allergy and immunology","volume":" ","pages":""},"PeriodicalIF":2.3000,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Prostaglandin E2 inhibits the differentiation of T regulatory cells by Peroxisome Proliferator-Activated Receptor-Gamma during allergic rhinitis.\",\"authors\":\"Yurong Ju, Lisha Li, Ye Zhao, Zhifeng Yang, Ziheng Zhao, Zhaofei Wu, Xuewen Pang, Wei Wang\",\"doi\":\"10.12932/AP-210923-1695\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Allergic rhinitis (AR) represents a significant global health concern that can give rise to numerous diseases and result in labor productivity. 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引用次数: 0
摘要
背景:过敏性鼻炎(AR)是一个全球关注的重大健康问题,可引发多种疾病并导致劳动生产率下降。T调节(Treg)细胞在过敏性鼻炎的发病机制中起着关键作用,其缺陷与前列腺素E2(PGE2)密切相关。然而,人们对这一关系的下游机制仍知之甚少:本研究旨在探讨 PGE2 影响 Treg 细胞分化的抑制机制:我们通过流式细胞术比较了在有或没有 PGE2 的情况下,AR 患者和健康对照组的幼稚 CD4+ T 细胞分化出的 Treg 细胞。检测了AR和健康供体Treg细胞中细胞内cAMP浓度、环-AMP依赖性蛋白激酶A(PKA)及其下游靶标过氧化物酶体增殖激活受体-γ(PPAR-γ)的mRNA和蛋白水平。通过花粉给药建立了 AR 小鼠模型:结果:PGE2通过EP4受体抑制了从人类幼稚CD4+ T细胞分化出的Treg细胞。此外,在 AR 患者和 AR 小鼠中观察到 EP4 受体表达增强。PGE2-EP4信号是通过激活cAMP-PKA信号通路产生的。随后,磷酸化的 PKA 会抑制 PPAR-γ 的表达。PPAR-γ激动剂吡格列酮可挽救Treg的分化,并有助于缓解AR小鼠模型的炎症:结论:在 AR 疾病中,PGE2-EP4 信号通过影响 cAMP-PKA 通路及其下游靶 PPAR-γ 对 Treg 的分化产生抑制作用。
Prostaglandin E2 inhibits the differentiation of T regulatory cells by Peroxisome Proliferator-Activated Receptor-Gamma during allergic rhinitis.
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.