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TH1 signatures are present in the lower airways of children with severe asthma, regardless of allergic status.
Wisniewski, Julia A; Muehling, Lyndsey M; Eccles, Jacob D; Capaldo, Brian J; Agrawal, Rachana; Shirley, Debbie-Ann; Patrie, James T; Workman, Lisa J; Schuyler, Alexander J; Lawrence, Monica G; Teague, W Gerald; Woodfolk, Judith A.
Afiliación
  • Wisniewski JA; Department of Medicine, University of Virginia School of Medicine, Charlottesville, Va; Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Va.
  • Muehling LM; Department of Medicine, University of Virginia School of Medicine, Charlottesville, Va.
  • Eccles JD; Department of Medicine, University of Virginia School of Medicine, Charlottesville, Va.
  • Capaldo BJ; Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, Va.
  • Agrawal R; Department of Medicine, University of Virginia School of Medicine, Charlottesville, Va.
  • Shirley DA; Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Va.
  • Patrie JT; Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, Va.
  • Workman LJ; Department of Medicine, University of Virginia School of Medicine, Charlottesville, Va.
  • Schuyler AJ; Department of Medicine, University of Virginia School of Medicine, Charlottesville, Va.
  • Lawrence MG; Department of Medicine, University of Virginia School of Medicine, Charlottesville, Va.
  • Teague WG; Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Va.
  • Woodfolk JA; Department of Medicine, University of Virginia School of Medicine, Charlottesville, Va. Electronic address: jaw4m@virginia.edu.
J Allergy Clin Immunol ; 141(6): 2048-2060.e13, 2018 06.
Article en En | MEDLINE | ID: mdl-28939412
BACKGROUND: The pathogenesis of severe asthma in childhood remains poorly understood. OBJECTIVE: We sought to construct the immunologic landscape in the airways of children with severe asthma. METHODS: Comprehensive analysis of multiple cell types and mediators was performed by using flow cytometry and a multiplex assay with bronchoalveolar lavage (BAL) specimens (n = 68) from 52 highly characterized allergic and nonallergic children (0.5-17 years) with severe treatment-refractory asthma. Multiple relationships were tested by using linear mixed-effects modeling. RESULTS: Memory CCR5+ TH1 cells were enriched in BAL fluid versus blood, and pathogenic respiratory viruses and bacteria were readily detected. IFN-γ+IL-17+ and IFN-γ-IL-17+ subsets constituted secondary TH types, and BAL fluid CD8+ T cells were almost exclusively IFN-γ+. The TH17-associated mediators IL-23 and macrophage inflammatory protein 3α/CCL20 were highly expressed. Despite low TH2 numbers, TH2 cytokines were detected, and TH2 skewing correlated with total IgE levels. Type 2 innate lymphoid cells and basophils were scarce in BAL fluid. Levels of IL-5, IL-33, and IL-28A/IFN-λ2 were increased in multisensitized children and correlated with IgE levels to dust mite, ryegrass, and fungi but not cat, ragweed, or food sources. Additionally, levels of IL-5, but no other cytokine, increased with age and correlated with eosinophil numbers in BAL fluid and blood. Both plasmacytoid and IgE+FcεRI+ myeloid dendritic cells were present in BAL fluid. CONCLUSIONS: The lower airways of children with severe asthma display a dominant TH1 signature and atypical cytokine profiles that link to allergic status. Our findings deviate from established paradigms and warrant further assessment of the pathogenicity of TH1 cells in patients with severe asthma.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Asma / Células TH1 Tipo de estudio: Prognostic_studies Límite: Adolescent / Child / Child, preschool / Female / Humans / Infant / Male Idioma: En Revista: J Allergy Clin Immunol Año: 2018 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Asma / Células TH1 Tipo de estudio: Prognostic_studies Límite: Adolescent / Child / Child, preschool / Female / Humans / Infant / Male Idioma: En Revista: J Allergy Clin Immunol Año: 2018 Tipo del documento: Article Pais de publicación: Estados Unidos