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Impact of high‐altitude therapy on type‐2 immune responses in asthma patients

机译:高原治疗对哮喘患者2型免疫应答的影响

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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 (nine eosinophilic allergic; EA, nine noneosinophilic allergic; NEA and eight noneosinophilic nonallergic; NN) and nine 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 chemoattractant receptor homolog expressed on Th2 cells (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.
机译:摘要背景哮喘患者存在与不同的免疫学曲线,具有2型子型的优势。本研究的目的是探讨高海拔治疗对哮喘临床和免疫应答的影响。方法方法二十六名住院治疗哮喘患者(九嗜酸性过敏; EA,九种非聚糖过敏; NEA和八种非聚氨酯非过性; NN)和9个健康对照在21岁的高海拔地区进行了入学。我们使用流式细胞术从外周血评估嗜酸性粒细胞,T细胞,Tregs和先天淋巴细胞(ILC)。结果在高度治疗后,在EA患者中,在TH2细胞(CRTH2)(CRTH2) - 表达CD4 +和CD8 + T细胞上表达的嗜酸性粒细胞(休息和活化)和化学侵入剂受体同源物的数量显着下降。在海拔地区治疗后,在所有哮喘表型和ILC2的频率下显着降低了Crth2 + Tregs的频率显着降低。在21℃以下的海拔治疗时,CrTh2表达ILC2,CD4 +和CD8 + T细胞和Treg细胞显示对外源PGD2的衰减响应。此外,发现通过CRTH2的PGD2信号传导来减小CRTH2 + Tregs的抑制功能,该抑制函数在高空处理期间部分归一化。在过敏性哮喘患者中,改善的哮喘控制尤其明显,并与EA患者中Crth2 + Treg细胞的频率下降相关。血清IL-5和IL-13在高基线水平的哮喘患者中的气候治疗期间减少。结论高海拔哮喘治疗减少了2型免疫应答,校正了CRTH2表达增加及其失调功能。

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