循环中CD4(+)CRTh2(+)T细胞水平升高是重度哮喘的特征。

Elevated levels of circulating CD4(+) CRTh2(+) T cells characterize severe asthma.

作者信息

Palikhe N S, Laratta C, Nahirney D, Vethanayagam D, Bhutani M, Vliagoftis H, Cameron L

机构信息

Pulmonary Research Group, Department of Medicine, University of Alberta, Edmonton, AB, Canada.

Department of Pathology and Laboratory Medicine, Schulich School of Medicine & Dentistry, Western University, London, ON, Canada.

出版信息

Clin Exp Allergy. 2016 Jun;46(6):825-36. doi: 10.1111/cea.12741.

DOI:10.1111/cea.12741

PMID:27079298

Abstract

BACKGROUND

Chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTh2) is a receptor for PGD2 and expressed by T cells, eosinophils, basophils, and ILC2 cells. CRTh2 expression by CD4(+) T cells identifies the Th2 subset, and these cells have been characterized as allergen-specific central memory Th2 cells. Recently, activation of the PGD2 -CRTh2 pathway in the lungs was associated with severe asthma.

OBJECTIVE

To assess circulating levels of Th2 cells and related mediators in severe asthma and those who experience asthma exacerbations.

METHODS

Peripheral blood cells expressing CRTh2 were characterized by flow cytometry and qRT-PCR. Serum IL-13 and PGD2 were measured by ELISA and compared with asthma severity and tendency to exacerbate.

RESULTS

Severe asthmatics had more circulating CD4(+) CRTh2(+) T cells, CRTh2 and GATA3 mRNA, and a higher level of serum IL-13 compared to mild/moderate asthmatics. The proportion of CD4(+) CRTh2(+) T cells was associated with lower lung function and was highest in severe asthmatics that exacerbated in the last year. Circulating CD4(+) CRTh2(+) T cells, unlike eosinophils, were positively correlated with inhaled steroid dose.

CONCLUSIONS AND CLINICAL RELEVANCE

Elevated levels of circulating CD4(+) CRTh2(+) T cells are a feature of severe asthma, despite high-dose corticosteroids. Tracking the systemic level of these cells may help identify type 2 severe asthmatics at risk of exacerbation.

摘要

背景

Th2细胞上表达的趋化因子受体同源分子（CRTh2）是前列腺素D2（PGD2）的受体，在T细胞、嗜酸性粒细胞、嗜碱性粒细胞和2型固有淋巴细胞（ILC2）中表达。CD4(+) T细胞表达CRTh2可识别Th2亚群，这些细胞已被鉴定为过敏原特异性中央记忆Th2细胞。最近，肺部PGD2-CRTh2途径的激活与重度哮喘相关。

目的

评估重度哮喘患者及哮喘急性加重患者体内Th2细胞及相关介质的循环水平。

方法

采用流式细胞术和定量逆转录聚合酶链反应（qRT-PCR）对表达CRTh2的外周血细胞进行鉴定。采用酶联免疫吸附测定（ELISA）法检测血清白细胞介素-13（IL-13）和PGD2水平，并与哮喘严重程度及急性加重倾向进行比较。

结果

与轻/中度哮喘患者相比，重度哮喘患者循环中的CD4(+) CRTh2(+) T细胞、CRTh2和GATA3信使核糖核酸（mRNA）更多，血清IL-13水平更高。CD4(+) CRTh2(+) T细胞比例与肺功能降低相关，在去年发生急性加重的重度哮喘患者中最高。与嗜酸性粒细胞不同，循环中的CD4(+) CRTh2(+) T细胞与吸入性糖皮质激素剂量呈正相关。