哮喘患者痰源上皮细胞与树突状细胞2型免疫靶标的共表达
2015/12/31
摘要
背景：无创痰标本可以识别哮喘患者的生物标记物。与全痰可能掩盖稀少细胞的改变及其细胞间的相互作用比较，痰中离散细胞群的研究可以提高测量的准确性。
目的：本文旨在通过富集痰源人类气道上皮细胞（sHBECs）和1型髓样树突状细胞（sDCs）来描述其与2型免疫应答相关的靶标转录共表达。
方法：采用病例-对照研究设计，病例组为轻度哮喘患者，对照组为健康人群。获取诱导痰后，通过流式细胞术同时富集sHBECs和sDCs。定量PCR用于测量sHBEC的胸腺基质淋巴细胞生成素（TSLP）、IL33和POSTN以及sDCs内下游靶标的mRNA，这些靶标包括OX40L、CCL17、PPP1R14A、CD1E、CD1b、CD80和CD86。
结果：最终纳入13例哮喘患者与11例对照组。哮喘患者sHBECs的TSLP（P=.001）、IL33（P=.05）和POSTN（P=.04）的mRNA表达增加。哮喘患者sDC的OX40L（P = .003）和CCL17（P = .0001）的mRNA表达增加。sHBEC TSLP mRNA的表达对sDC OX40L mRNA的表达有明显影响（R = 0.65, P = .001），同时对CCLl7 mRNA的表达有影响。sHBECIL33mRNA的表达对sDC OX40L mRNA的表达有影响，而对sDCCCL17则无影响。
结论：通过富集来自无创痰标本中选择的细胞群，可以使我们对哮喘患者中细胞与细胞间的相互作用了解更深入，也有潜力提升哮喘患者的内在分型。
Coexpression of type 2 immune targets in sputum-derived epithelial and dendritic cells from asthmatic subjects
Bleck B; Kazeros A; Bakal K; Garcia-Medina L; Adams A; Liu M; Lee RA; Tse DB; Chiu A; Grunig G; Egan JP 3rd; Reibman J.
J Allergy Clin Immunol; 2015 Sep; 136(3):619-627.
ABSTRACT
Background: Noninvasive sputum sampling has enabled the identification of biomarkers in asthmatic patients. Studies of discrete cell populations in sputum can enhance measurements compared with whole sputum in which changes in rare cells and cell-cell interactions can be masked.
Objective: We sought to enrich for sputum-derived human bronchial epithelial cells (sHBECs) and sputum-derived myeloid type 1 dendritic cells (sDCs) to describe transcriptional coexpression of targets associated with a type 2 immune response.
Methods: A case-control study was conducted with patients with mild asthma (asthmatic cases) and healthy control subjects. Induced sputum was obtained for simultaneous enrichment of sHBECs and sDCs by using flow cytometry. Quantitative PCR was used to measure mRNA for sHBEC thymic stromal lymphopoietin (TSLP), IL33, POSTN, and IL25 and downstream targets in sDCs (OX40 ligand [OX40L], CCL17, PPP1R14A, CD1E, CD1b, CD80, and CD86).
Results: Final analyses for the study sample were based on 11control subjects and 13 asthmatic cases. Expression of TSLP, IL33, and POSTN Mrna was increased in sHBECs in asthmatic cases (P = .001, P = .05, and P= .04, respectively). Expression of sDC OX40L and CCL17 mRNA was increased in asthmatic cases (P= .003 and P= .0001, respectively). sHBEC TSLP mRNA expression was strongly associated with sDC OX40LmRNA expression (R= 0.65, P= .001) and less strongly with sDC CCL17 mRNA expression. sHBEC IL33 mRNA expression was associated with sDC OX40L mRNA expression (R= 0.42,P= .04) but not sDC CCL17 mRNA expression.
Conclusions: Noninvasive sampling and enrichment of select cell populations from sputum can further our understanding of cell-cell interactions in asthmatic patients with the potential to enhance endotyping of asthmatic patients.
背景：无创痰标本可以识别哮喘患者的生物标记物。与全痰可能掩盖稀少细胞的改变及其细胞间的相互作用比较，痰中离散细胞群的研究可以提高测量的准确性。
目的：本文旨在通过富集痰源人类气道上皮细胞（sHBECs）和1型髓样树突状细胞（sDCs）来描述其与2型免疫应答相关的靶标转录共表达。
方法：采用病例-对照研究设计，病例组为轻度哮喘患者，对照组为健康人群。获取诱导痰后，通过流式细胞术同时富集sHBECs和sDCs。定量PCR用于测量sHBEC的胸腺基质淋巴细胞生成素（TSLP）、IL33和POSTN以及sDCs内下游靶标的mRNA，这些靶标包括OX40L、CCL17、PPP1R14A、CD1E、CD1b、CD80和CD86。
结果：最终纳入13例哮喘患者与11例对照组。哮喘患者sHBECs的TSLP（P=.001）、IL33（P=.05）和POSTN（P=.04）的mRNA表达增加。哮喘患者sDC的OX40L（P = .003）和CCL17（P = .0001）的mRNA表达增加。sHBEC TSLP mRNA的表达对sDC OX40L mRNA的表达有明显影响（R = 0.65, P = .001），同时对CCLl7 mRNA的表达有影响。sHBECIL33mRNA的表达对sDC OX40L mRNA的表达有影响，而对sDCCCL17则无影响。
结论：通过富集来自无创痰标本中选择的细胞群，可以使我们对哮喘患者中细胞与细胞间的相互作用了解更深入，也有潜力提升哮喘患者的内在分型。
(王霁 张红萍 王刚 四川大学华西医院中西医结合科呼吸病组 610041 摘译)
（J Allergy Clin Immunol; 2015 Sep; 136(3):619-627.）
（J Allergy Clin Immunol; 2015 Sep; 136(3):619-627.）
Coexpression of type 2 immune targets in sputum-derived epithelial and dendritic cells from asthmatic subjects
Bleck B; Kazeros A; Bakal K; Garcia-Medina L; Adams A; Liu M; Lee RA; Tse DB; Chiu A; Grunig G; Egan JP 3rd; Reibman J.
J Allergy Clin Immunol; 2015 Sep; 136(3):619-627.
ABSTRACT
Background: Noninvasive sputum sampling has enabled the identification of biomarkers in asthmatic patients. Studies of discrete cell populations in sputum can enhance measurements compared with whole sputum in which changes in rare cells and cell-cell interactions can be masked.
Objective: We sought to enrich for sputum-derived human bronchial epithelial cells (sHBECs) and sputum-derived myeloid type 1 dendritic cells (sDCs) to describe transcriptional coexpression of targets associated with a type 2 immune response.
Methods: A case-control study was conducted with patients with mild asthma (asthmatic cases) and healthy control subjects. Induced sputum was obtained for simultaneous enrichment of sHBECs and sDCs by using flow cytometry. Quantitative PCR was used to measure mRNA for sHBEC thymic stromal lymphopoietin (TSLP), IL33, POSTN, and IL25 and downstream targets in sDCs (OX40 ligand [OX40L], CCL17, PPP1R14A, CD1E, CD1b, CD80, and CD86).
Results: Final analyses for the study sample were based on 11control subjects and 13 asthmatic cases. Expression of TSLP, IL33, and POSTN Mrna was increased in sHBECs in asthmatic cases (P = .001, P = .05, and P= .04, respectively). Expression of sDC OX40L and CCL17 mRNA was increased in asthmatic cases (P= .003 and P= .0001, respectively). sHBEC TSLP mRNA expression was strongly associated with sDC OX40LmRNA expression (R= 0.65, P= .001) and less strongly with sDC CCL17 mRNA expression. sHBEC IL33 mRNA expression was associated with sDC OX40L mRNA expression (R= 0.42,P= .04) but not sDC CCL17 mRNA expression.
Conclusions: Noninvasive sampling and enrichment of select cell populations from sputum can further our understanding of cell-cell interactions in asthmatic patients with the potential to enhance endotyping of asthmatic patients.
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伴或不伴特应性疾病的儿童哮喘临床特征与严重程度分析：一项横断面研究
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早发型及迟发型哮喘的不同严重程度和严重程度预测: 一项来自台湾的基于人群的研究
