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

Autor:	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., 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., 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., 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., Mohanty C; Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI 53726, USA., Kendziorski C; Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI 53726, USA., 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., 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., Ober C; Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA., 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., 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., 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.
Jazyk:	angličtina
Zdroj:	Cell genomics [Cell Genom] 2024 Sep 11; Vol. 4 (9), pp. 100636. Date of Electronic Publication: 2024 Aug 27.
DOI:	10.1016/j.xgen.2024.100636
Abstrakt:	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. Competing Interests: 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. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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