title: Coexpression of type 2 immune targets in sputum-derived epithelial and dendritic cells from asthmatic subjects.
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 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.
  
  
  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.
authors: Department of Medicine, New York University Langone Medical Center, New York, NY.
authors: Bertram
authors: B
authors: Bleck
authors: Department of Medicine, New York University Langone Medical Center, New York, NY.
authors: Angeliki
authors: A
authors: Kazeros
authors: Department of Medicine, New York University Langone Medical Center, New York, NY.
authors: Keren
authors: K
authors: Bakal
authors: Department of Medicine, New York University Langone Medical Center, New York, NY.
authors: Lymaris
authors: L
authors: Garcia-Medina
authors: Department of Medicine, New York University Langone Medical Center, New York, NY.
authors: Alexandra
authors: A
authors: Adams
authors: Department of Environmental Medicine, New York University Langone Medical Center, New York, NY; Population Health, New York University School of Medicine, New York, NY.
authors: Mengling
authors: M
authors: Liu
authors: Department of Medicine, New York University Langone Medical Center, New York, NY.
authors: Richard A
authors: RA
authors: Lee
authors: Department of Medicine, New York University Langone Medical Center, New York, NY.
authors: Doris B
authors: DB
authors: Tse
authors: Department of Medicine, New York University Langone Medical Center, New York, NY.
authors: Amanda
authors: A
authors: Chiu
authors: Department of Environmental Medicine, New York University Langone Medical Center, New York, NY.
authors: Gabriele
authors: G
authors: Grunig
authors: Department of Medicine, New York University Langone Medical Center, New York, NY.
authors: John P
authors: JP
authors: Egan
authors: Department of Medicine, New York University Langone Medical Center, New York, NY; Department of Environmental Medicine, New York University Langone Medical Center, New York, NY. Electronic address: Joan.Reibman@nyumc.org.
authors: Joan
authors: J
authors: Reibman
mesh_terms: D000328:Adult; D018949:Antigens, CD1 / Q000235:genetics / Q000276:immunology; D001249:Asthma / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology; D051940:B7-2 Antigen / Q000235:genetics / Q000276:immunology; D016022:Case-Control Studies; D002450:Cell Communication; D054414:Chemokine CCL17 / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology; D000067596:Interleukin-33 / Q000235:genetics / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins; D053278:OX40 Ligand / Q000235:genetics / Q000276:immunology; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013183:Sputum / Q000166:cytology
chemical_list: D018949:Antigens, CD1; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C106230:CCL17 protein, human; C419394:CD1b antigen; C417738:CD1e antigen; C497964:CD86 protein, human; D054414:Chemokine CCL17; C486701:IL25 protein, human; C506536:IL33 protein, human; D020381:Interleukin-17; D000067596:Interleukin-33; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D053278:OX40 Ligand; C107507:PPP1R14A protein, human; C089251:TNFSF4 protein, human; D010749:Phosphoprotein Phosphatases
keywords: Asthma; CCL17; IL-33; OX40 ligand; bronchial epithelial cells; dendritic cells; sputum; thymic stromal lymphopoietin