title: Soluble major histocompatibility complex class I-related chain B molecules are increased and correlate with clinical outcomes during rhinovirus infection in healthy subjects.
abstract: BACKGROUND
  Surface major histocompatibility complex class I-related chain (MIC) A and B molecules are increased by IL-15 and have a role in the activation of natural killer group 2 member D-positive natural killer and CD8 T cells. MICA and MICB also exist in soluble forms (sMICA and sMICB). Rhinoviruses (RVs) are the major cause of asthma exacerbations, and IL-15 levels are decreased in the airways of subjects with asthma. The role of MIC molecules in immune responses in the lung has not been studied. Here, we determine the relationship between MICA and MICB and RV infection in vitro in respiratory epithelial cells and in vivo in healthy subjects and subjects with asthma.
  
  
  METHODS
  Surface MICA and MICB, as well as sMICA and sMICB, in respiratory epithelial cells were measured in vitro in response to RV infection and exposure to IL-15. Levels of sMICA and sMICB in serum, sputum, and BAL were measured and correlated with blood and bronchoalveolar immune cells in healthy subjects and subjects with asthma before and during RV infection.
  
  
  RESULTS
  RV increased MICA and MICB in vitro in epithelial cells. Exogenous IL-15 upregulated sMICB levels in RV-infected epithelial cells. Levels of sMICB molecules in serum were increased in healthy subjects compared with subjects with stable asthma. Following RV infection, airway levels of sMIC are upregulated, and there are positive correlations between sputum MICB levels and the percentage of bronchoalveolar natural killer cells in healthy subjects but not subjects with asthma.
  
  
  CONCLUSIONS
  RV infection induces MIC molecules in respiratory epithelial cells in vitro and in vivo. Induction of MICB molecules is impaired in subjects with asthma, suggesting these molecules may have a role in the antiviral immune response to RV infections.
authors.affiliation: Airways Disease Infection Section, National Heart & Lung Institute (NHLI), and Centre for Respiratory Infection, Imperial College London, London, England.
authors.forename: Aurica G
authors.initials: AG
authors.lastname: Telcian
authors.affiliation: Medical Research Council, London, England; Asthma UK Centre in Allergic Mechanisms of Asthma, London, England; The Oncology Institute "Prof. Dr. Ion Chiricuţă" Cluj-Napoca and Iuliu Haţieganu University of Medicine and Pharmacy Cluj-Napoca, Cluj-Napoca, Romania. Electronic address: mzdrenghea@umfcluj.ro.
authors.forename: Mihnea T
authors.initials: MT
authors.lastname: Zdrenghea
authors.affiliation: Centro Interdipartimentale per lo Studio delle Malattie Infiammatorie delle Vie Aeree e Patologie Fumo-correlate (CEMICEF), Sezione di Malattie dell'Apparato Respiratorio, Università degli Studi di Ferrara, Ferrara, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Caramori
authors.affiliation: Airways Disease Infection Section, National Heart & Lung Institute (NHLI), and Centre for Respiratory Infection, Imperial College London, London, England.
authors.forename: Vasile
authors.initials: V
authors.lastname: Laza-Stanca
authors.affiliation: Airways Disease Infection Section, National Heart & Lung Institute (NHLI), and Centre for Respiratory Infection, Imperial College London, London, England; Imperial College Healthcare NHS Trust, London, England.
authors.forename: Simon D
authors.initials: SD
authors.lastname: Message
authors.affiliation: Airways Disease Infection Section, National Heart & Lung Institute (NHLI), and Centre for Respiratory Infection, Imperial College London, London, England.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Kebadze
authors.affiliation: Imperial College Healthcare NHS Trust, London, England.
authors.forename: Onn M
authors.initials: OM
authors.lastname: Kon
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Veronika
authors.initials: V
authors.lastname: Groh
authors.affiliation: Centro Interdipartimentale per lo Studio delle Malattie Infiammatorie delle Vie Aeree e Patologie Fumo-correlate (CEMICEF), Sezione di Malattie dell'Apparato Respiratorio, Università degli Studi di Ferrara, Ferrara, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Papi
authors.affiliation: Airways Disease Infection Section, National Heart & Lung Institute (NHLI), and Centre for Respiratory Infection, Imperial College London, London, England; Imperial College Healthcare NHS Trust, London, England.
authors.forename: Sebastian L
authors.initials: SL
authors.lastname: Johnston
authors.affiliation: Airways Disease Infection Section, National Heart & Lung Institute (NHLI), and Centre for Respiratory Infection, Imperial College London, London, England; Imperial College Healthcare NHS Trust, London, England.
authors.forename: Patrick
authors.initials: P
authors.lastname: Mallia
authors.affiliation: Airways Disease Infection Section, National Heart & Lung Institute (NHLI), and Centre for Respiratory Infection, Imperial College London, London, England; Medical Research Council, London, England; Asthma UK Centre in Allergic Mechanisms of Asthma, London, England; The Oncology Institute "Prof. Dr. Ion Chiricuţă" Cluj-Napoca and Iuliu Haţieganu University of Medicine and Pharmacy Cluj-Napoca, Cluj-Napoca, Romania.
authors.forename: Luminita A
authors.initials: LA
authors.lastname: Stanciu
mesh_terms: D000328:Adult; D001249:Asthma / Q000150:complications / Q000276:immunology / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002478:Cells, Cultured; D005260:Female; D015796:HLA-B27 Antigen / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007111:Immunity, Cellular; D019409:Interleukin-15 / Q000378:metabolism; D008297:Male; D010850:Picornaviridae Infections / Q000150:complications / Q000276:immunology / Q000378:metabolism*; D012016:Reference Values; D020545:Respiratory Mucosa / Q000378:metabolism / Q000473:pathology / Q000821:virology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: C090660:HLA-B protein, human; D015796:HLA-B27 Antigen; D019409:Interleukin-15