重度哮喘患者免疫反应性胸腺基质淋巴细胞生成素表达增加
2011/11/22
摘要
背景:胸腺基质淋巴细胞生成素(TSLP)是一种细胞因子,通过2个不同的途径参与哮喘的病理生理过程:TSLP-OX40配体(OX40L)-T细胞轴、TSLP-肥大细胞轴。哮喘患者中是否也存在这些通路的活化尚不清楚。
目的:研究粘膜TSLP蛋白表达与哮喘严重程度的关系及其TSLP的不同免疫通路。
方法:健康个体和中度至重度哮喘患者入选。对支气管活检样本进行免疫染色,检测TSLP、OX40、OX40L、 T(H)2细胞因子和炎症细胞标志物的表达。采用RNA芯片和定量RT-PCR检测基因表达。
结果:哮喘患者间的TSLP、IL-13和IL-4表达水平存在着显著差异。总体来说,哮喘患者的气道上皮细胞和固有层TSLP蛋白表达显著增加,重度哮喘患者尤其明显。气道上皮细胞和固有层的TSLP表达与气流梗阻的严重程度相关。大部分表达IL-13的白细胞可能是nuocyte细胞。考虑到患者间变异,固有层IL-13表达增加的哮喘患者中,55%的患者IL-4和TSLP表达也增加。而且支气管活检标本中TSLP基因表达、Th2因子基因表达以及嗜酸性粒细胞炎症间存在显著相关性。活检样本的OX40、 OX40L和CD83表达较低,而且哮喘患者与健康个体间无显著差异。
结论:重度哮喘患者的TSLP表达水平即使在高剂量激素吸入或口服治疗后仍然显著增加。TSLP靶向治疗可能仅对存在TSLP表达增加和Th2炎症的哮喘患者有效。
(林江涛 审校)
J Allergy Clin Immunol. 2011 Oct 3. [Epub ahead of print]
Increased expression of immunoreactive thymic stromal lymphopoietin in patients with severe asthma.
Shikotra A, Choy DF, Ohri CM, Doran E, Butler C, Hargadon B, Shelley M, Abbas AR, Austin CD, Jackman J, Wu LC, Heaney LG, Arron JR, Bradding P.
Source
Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom.
Abstract
BACKGROUND: Thymic stromal lymphopoietin (TSLP) is a cytokine implicated in the pathophysiology of asthma through 2 distinct pathways: a TSLP-OX40 ligand (OX40L)-T cell axis and a TSLP-mast cell axis. Whether these pathways are active in human asthma is unknown.
OBJECTIVE: We sought to investigate whether mucosal TSLP protein expression relates to asthma severity and distinct immunologic pathways.
METHODS: In healthy subjects and patients with mild-to-severe asthma, we immunostained bronchial biopsy specimens for TSLP, OX40, OX40L, T(H)2 cytokines, and inflammatory cell markers. We examined gene expression using RNA microarrays and quantitative RT-PCR.
RESULTS: There was considerable heterogeneity in the levels of TSLP, IL-13, and IL-4 immunostaining across the cohort of asthmatic patients examined. Overall, TSLP protein expression was significantly increased in airway epithelium and lamina propria of asthmatic patients, particularly in patients with severe asthma. TSLP immunostaining in both compartments correlated with the severity of airflow obstruction. The majority of leukocytes expressing IL-13 were possibly nuocytes. Accounting for intersubject variability, the 55% of asthmatic patients with increased IL-13 immunostaining in the lamina propria also had increased IL-4 and TSLP expression. This was further substantiated by significant correlations between TSLP gene expression, a T(H)2 gene expression signature, and eosinophilic inflammation in bronchial biopsy specimens. Immunostaining for OX40, OX40L, and CD83 was sparse, with no difference between asthmatic patients and healthy subjects.
CONCLUSION: TSLP expression is increased in a subset of patients with severe asthma in spite of high-dose inhaled or oral corticosteroid therapy. Targeting TSLP might only be efficacious in the subset of asthma characterized by increased TSLP expression and T(H)2 inflammation.
J Allergy Clin Immunol. 2011 Oct 3. [Epub ahead of print]