Transcriptome networks identify mechanisms of viral and nonviral asthma exacerbations in children.

Autor: Altman MC; Department of Allergy and Infectious Diseases, University of Washington, Seattle, WA, USA. maltman@benaroyaresearch.org.; Systems Immunology Program, Benaroya Research Institute, Seattle, WA, USA. maltman@benaroyaresearch.org., Gill MA; Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA., Whalen E; Systems Immunology Program, Benaroya Research Institute, Seattle, WA, USA., Babineau DC; Rho, Inc., Chapel Hill, NC, USA., Shao B; Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA., Liu AH; Department of Allergy and Immunology, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, CO, USA., Jepson B; Rho, Inc., Chapel Hill, NC, USA., Gruchalla RS; Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA., O'Connor GT; Department of Medicine, Boston University School of Medicine, Boston, MA, USA., Pongracic JA; Ann Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA., Kercsmar CM; Cincinnati Children's Hospital, Cincinnati, OH, USA., Khurana Hershey GK; Cincinnati Children's Hospital, Cincinnati, OH, USA., Zoratti EM; Henry Ford Health System, Detroit, MI, USA., Johnson CC; Henry Ford Health System, Detroit, MI, USA., Teach SJ; Children's National Health System, Washington, DC, USA., Kattan M; Columbia University College of Physicians and Surgeons, New York, NY, USA., Bacharier LB; Division of Allergy, Immunology, and Pulmonary Medicine, Washington University, St. Louis, MO, USA., Beigelman A; Division of Allergy, Immunology, and Pulmonary Medicine, Washington University, St. Louis, MO, USA., Sigelman SM; Division of Allergy, Immunology, and Transplantation, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA., Presnell S; Systems Immunology Program, Benaroya Research Institute, Seattle, WA, USA., Gern JE; University of Wisconsin School of Medicine and Public Health, Madison, WI, USA., Gergen PJ; Division of Allergy, Immunology, and Transplantation, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA., Wheatley LM; Division of Allergy, Immunology, and Transplantation, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA., Togias A; Division of Allergy, Immunology, and Transplantation, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA., Busse WW; University of Wisconsin School of Medicine and Public Health, Madison, WI, USA., Jackson DJ; University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Jazyk: angličtina
Zdroj: Nature immunology [Nat Immunol] 2019 May; Vol. 20 (5), pp. 637-651. Date of Electronic Publication: 2019 Apr 08.
DOI: 10.1038/s41590-019-0347-8
Abstrakt: Respiratory infections are common precursors to asthma exacerbations in children, but molecular immune responses that determine whether and how an infection causes an exacerbation are poorly understood. By using systems-scale network analysis, we identify repertoires of cellular transcriptional pathways that lead to and underlie distinct patterns of asthma exacerbation. Specifically, in both virus-associated and nonviral exacerbations, we demonstrate a set of core exacerbation modules, among which epithelial-associated SMAD3 signaling is upregulated and lymphocyte response pathways are downregulated early in exacerbation, followed by later upregulation of effector pathways including epidermal growth factor receptor signaling, extracellular matrix production, mucus hypersecretion, and eosinophil activation. We show an additional set of multiple inflammatory cell pathways involved in virus-associated exacerbations, in contrast to squamous cell pathways associated with nonviral exacerbations. Our work introduces an in vivo molecular platform to investigate, in a clinical setting, both the mechanisms of disease pathogenesis and therapeutic targets to modify exacerbations.
Databáze: MEDLINE