Coexpression of type 2 immune targets in sputum-derived epithelial and dendritic cells from asthmatic subjects

• Published in: Journal of allergy and clinical immunology Vol. 136; no. 3; pp. 619 - 627.e5
• Main Authors: Bleck, Bertram, Kazeros, Angeliki, Bakal, Keren, Garcia-Medina, Lymaris, Adams, Alexandra, Liu, Mengling, Lee, Richard A., Tse, Doris B., Chiu, Amanda, Grunig, Gabriele, Egan, John P., Reibman, Joan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2015; Elsevier Limited
• Subjects: Adult; Allergy and Immunology; Antigens, CD1 - genetics; Antigens, CD1 - immunology; Asthma; Asthma - genetics; Asthma - immunology; Asthma - pathology; B7-1 Antigen - genetics; B7-1 Antigen - immunology; B7-2 Antigen - genetics; B7-2 Antigen - immunology; bronchial epithelial cells; Case-Control Studies; CCL17; Cell Communication; Chemokine CCL17 - genetics; Chemokine CCL17 - immunology; Cytokines; Dendritic cells; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dendritic Cells - pathology; Epithelial Cells - immunology; Epithelial Cells - metabolism; Epithelial Cells - pathology; Ethnicity; Female; Gene Expression; Gene Expression Profiling; Human subjects; Humans; IL-33; Inflammation; Interleukin-17 - genetics; Interleukin-17 - immunology; Interleukin-33 - genetics; Interleukin-33 - immunology; Laboratories; Male; Middle Aged; OX40 ligand; OX40 Ligand - genetics; OX40 Ligand - immunology; Phosphoprotein Phosphatases - genetics; Phosphoprotein Phosphatases - immunology; Signal Transduction - genetics; Signal Transduction - immunology; sputum; Sputum - cytology; Studies; thymic stromal lymphopoietin; SSC; bronchial epithelial cells; TSLP; OX40L; sputum; FACS; IQR; IL-33; CK-7; EGFR; Asthma; Ct; thymic stromal lymphopoietin; dendritic cells; OX40 ligand; sDC; FSC; qPCR; CCL17; GAPDH; sHBEC; DC; Gyceraldehyde-3-phosphate dehydrogenase; Epidermal growth factor receptor; Dendritic cell; Sputum-derived human bronchial epithelial cell; Cytokeratin-7; Quantitative PCR; Side scatter; Fluorescence-activated cell sorting; Sputum-derived myeloid type 1 dendritic cell; Interquartile range; Cycle threshold; Forward scatter
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2014.12.1950

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. 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. 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). Final analyses for the study sample were based on 11 control 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 OX40L mRNA 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. 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.