高原治疗对哮喘患者2型免疫应答的影响
2019/07/11
摘要
背景:哮喘患者具有以2型內型为主的免疫学特征。本研究旨在探讨高原治疗对哮喘临床及免疫应答的影响。
方法:对26例住院哮喘患者(9例嗜酸性粒细胞性过敏性;EA,9例非嗜酸性粒细胞性过敏性;NEA,8例非嗜酸性粒细胞性非过敏性;NN)和9例高原健康对照者进行为期21天的研究。我采用流式细胞术评估外周血嗜酸性粒细胞、T细胞、Tregs和先天淋巴细胞(ILC)。
结果:高原治疗后EA患者嗜酸性粒细胞(静息和活化)和CRTH2表达的CD4+和CD8+T细胞数量明显减少。在所有哮喘表型中,经高原治疗后EA患者的CRTH2+Tregs频率和ILC2的频率均显著降低。经过21天的高原治疗后,表达ILC2的CRTH2,CD4+和CD8+T细胞以及Treg细胞对外源性PGD2的反应减弱。此外,通过CRTH2的PGD2信号降低了CRTH2+Treg的抑制功能,后者在高原治疗过程中部分正常化。改善哮喘控制在过敏性哮喘患者中尤为明显,并与EA患者CRTH2+Treg细胞频率降低相关。血清IL-5和IL-13在高基线哮喘患者的治疗中降低。
结论:高原哮喘治疗降低了2型免疫应答,纠正了CRTH2表达的增加及功能失调。
(中日友好医院呼吸与危重症医学科 张清 摘译 林江涛 审校)
(Allergy. 2019 Jul 3. doi: 10.1111/all.13967.)
Impact of High Altitude Therapy on Type-2 Immune Responses in Asthma Patients.
Boonpiyathad T, Capova G, Duchna HW, Croxford AL, Farine H, Dreher A, Clozel M, Schreiber J, Kubena P, Lunjani N, Mirer D, Rückert B, Satitsuksanoa P, Tan G, Groenen PMA, Akdis M, Strasser DS, Renner ED, Akdis CA.
Abstract
BACKGROUND:Asthma patients present with distinct immunological profiles, with a predominance of type 2 endotype. The aim of this study was to investigate the impact of high altitude treatment on the clinical and immunological response in asthma.
Methods:Twenty-six hospitalized asthma patients (9 eosinophilic allergic; EA, 9 non-eosinophilic allergic; NEA and 8 non-eosinophilic non-allergic; NN) and 9 healthy controls in high-altitude for 21 days were enrolled in the study. We assessed eosinophils, T cells, Tregs, and innate lymphoid cells (ILC) from peripheral blood using flow cytometry.
RESULTS:The number of eosinophils (both resting and activated) and CRTH2-expressing CD4+ and CD8+ T cells decreased significantly in EA patients after altitude treatment. The frequency of CRTH2+ Tregs as decreased significantly in all the asthma phenotypes as well as the frequency of ILC2 was significantly reduced in EA after altitude treatment. After 21 days of altitude therapy, CRTH2-expressing ILC2, CD4+and CD8+ T cells and Treg cells showed attenuated responses to exogenous PGD2. Furthermore, PGD2 signaling via CRTH2 was found to diminish the suppressive function of CRTH2+ Tregs which partially normalized during high altitude treatment. Improved asthma control was particularly evident in allergic asthma patients and correlated with decreased frequencies of CRTH2+ Treg cells in EA patients. Serum IL-5 and IL-13 decreased during climate treatment in asthma patients with high baseline levels.
Conclusions:Asthma treatment in high altitude reduced the type 2 immune response, corrected the increased CRTH2 expression and its dysregulated functions. This article is protected by copyright. All rights reserved.
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