Rhinovirus infection of airway epithelial cells uncovers the non-ciliated subset as a likely driver of genetic risk to childhood-onset asthma.

airway epithelial cells asthma gene by environment genome-wide association study genomics rhinovirus transcriptomics

Journal

Cell genomics
ISSN: 2666-979X
Titre abrégé: Cell Genom
Pays: United States
ID NLM: 9918284260106676

Informations de publication

Date de publication:
21 Aug 2024
Historique:
received: 27 01 2024
revised: 11 06 2024
accepted: 01 08 2024
medline: 31 8 2024
pubmed: 31 8 2024
entrez: 28 8 2024
Statut: aheadofprint

Résumé

Asthma is a complex disease caused by genetic and environmental factors. Studies show that wheezing during rhinovirus infection correlates with childhood asthma development. Over 150 non-coding risk variants for asthma have been identified, many affecting gene regulation in T cells, but the effects of most risk variants remain unknown. We hypothesized that airway epithelial cells could also mediate genetic susceptibility to asthma given they are the first line of defense against respiratory viruses and allergens. We integrated genetic data with transcriptomics of airway epithelial cells subject to different stimuli. We demonstrate that rhinovirus infection significantly upregulates childhood-onset asthma-associated genes, particularly in non-ciliated cells. This enrichment is also observed with influenza infection but not with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or cytokine activation. Overall, our results suggest that rhinovirus infection is an environmental factor that interacts with genetic risk factors through non-ciliated airway epithelial cells to drive childhood-onset asthma.

Identifiants

DOI: 10.1016/j.xgen.2024.100636 PMID: 39197446
pubmed: 39197446
pii: S2666-979X(24)00240-4
doi: 10.1016/j.xgen.2024.100636
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

100636

Informations de copyright

Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests J.A.B. has served on scientific advisory boards for Siolta Therapeutics, Third Harmonic Bio, and Sanofi/Aventis. N.A.B. has served on scientific advisory boards for Regeneron.

Auteurs

Sarah Djeddi (S)

Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Daniela Fernandez-Salinas (D)

Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Licenciatura en Ciencias Genómicas, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Cuernavaca, Morelos 62210, México.

George X Huang (GX)

Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; Jeff and Penny Vinik Center for Allergic Disease Research, Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, MA 02115, USA.

Vitor R C Aguiar (VRC)

Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Chitrasen Mohanty (C)

Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI 53726, USA.

Christina Kendziorski (C)

Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI 53726, USA.

Steven Gazal (S)

Department of Quantitative and Computational Biology, University of Southern California, Los Angeles, CA 90007, USA; Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90007, USA.

Joshua A Boyce (JA)

Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; Jeff and Penny Vinik Center for Allergic Disease Research, Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, MA 02115, USA.

Carole Ober (C)

Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA.

James E Gern (JE)

Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI 53726, USA; Departments of Pediatrics and Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53726, USA.

Nora A Barrett (NA)

Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; Jeff and Penny Vinik Center for Allergic Disease Research, Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, MA 02115, USA.

Maria Gutierrez-Arcelus (M)

Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: mgutierr@broadinstitute.org.

Classifications MeSH