IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-33882-w.html
   My bibliography  Save this article

Epithelial coxsackievirus adenovirus receptor promotes house dust mite-induced lung inflammation

Author

Listed:
  • Elena Ortiz-Zapater

    (King’s College London
    School of Immunology and Microbial Science King’s College London)

  • Dustin C. Bagley

    (King’s College London)

  • Virginia Llopis Hernandez

    (King’s College London)

  • Luke B. Roberts

    (King’s College London)

  • Thomas J. A. Maguire

    (King’s College London)

  • Felizia Voss

    (Max-Delbrück-Centrum für Molekulare Medizin in the Helmholtz Assoziation (MDC)
    DZHK Partner site Berlin)

  • Philipp Mertins

    (Max Delbrück Center for Molecular Medicine (MDC))

  • Marieluise Kirchner

    (Max Delbrück Center for Molecular Medicine (MDC))

  • Isabel Peset-Martin

    (Alderley Park, Macclesfield)

  • Grzegorz Woszczek

    (King’s College London)

  • Jody Rosenblatt

    (King’s College London)

  • Michael Gotthardt

    (Max-Delbrück-Centrum für Molekulare Medizin in the Helmholtz Assoziation (MDC)
    Max Delbrück Center for Molecular Medicine (MDC)
    Charité Universitätsmedizin Berlin)

  • George Santis

    (School of Immunology and Microbial Science King’s College London
    Guy’s & St Thomas NHS Trust)

  • Maddy Parsons

    (King’s College London)

Abstract

Airway inflammation and remodelling are important pathophysiologic features in asthma and other respiratory conditions. An intact epithelial cell layer is crucial to maintain lung homoeostasis, and this depends on intercellular adhesion, whilst damaged respiratory epithelium is the primary instigator of airway inflammation. The Coxsackievirus Adenovirus Receptor (CAR) is highly expressed in the epithelium where it modulates cell-cell adhesion stability and facilitates immune cell transepithelial migration. However, the contribution of CAR to lung inflammation remains unclear. Here we investigate the mechanistic contribution of CAR in mediating responses to the common aeroallergen, House Dust Mite (HDM). We demonstrate that administration of HDM in mice lacking CAR in the respiratory epithelium leads to loss of peri-bronchial inflammatory cell infiltration, fewer goblet-cells and decreased pro-inflammatory cytokine release. In vitro analysis in human lung epithelial cells confirms that loss of CAR leads to reduced HDM-dependent inflammatory cytokine release and neutrophil migration. Epithelial CAR depletion also promoted smooth muscle cell proliferation mediated by GSK3β and TGF-β, basal matrix production and airway hyperresponsiveness. Our data demonstrate that CAR coordinates lung inflammation through a dual function in leucocyte recruitment and tissue remodelling and may represent an important target for future therapeutic development in inflammatory lung diseases.

Suggested Citation

  • Elena Ortiz-Zapater & Dustin C. Bagley & Virginia Llopis Hernandez & Luke B. Roberts & Thomas J. A. Maguire & Felizia Voss & Philipp Mertins & Marieluise Kirchner & Isabel Peset-Martin & Grzegorz Wosz, 2022. "Epithelial coxsackievirus adenovirus receptor promotes house dust mite-induced lung inflammation," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33882-w
    DOI: 10.1038/s41467-022-33882-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-33882-w
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-33882-w?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Franziska Rudolph & Claudia Fink & Judith Hüttemeister & Marieluise Kirchner & Michael H. Radke & Jacobo Lopez Carballo & Eva Wagner & Tobias Kohl & Stephan E. Lehnart & Philipp Mertins & Michael Gott, 2020. "Deconstructing sarcomeric structure–function relations in titin-BioID knock-in mice," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    2. Khondoker M. Akram & Laura L. Yates & Róisín Mongey & Stephen Rothery & David C. A. Gaboriau & Jeremy Sanderson & Matthew Hind & Mark Griffiths & Charlotte H. Dean, 2019. "Live imaging of alveologenesis in precision-cut lung slices reveals dynamic epithelial cell behaviour," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Haibo Zhang & Keke Xue & Wen Li & Xinyi Yang & Yusen Gou & Xiao Su & Feng Qian & Lei Sun, 2024. "Cullin5 drives experimental asthma exacerbations by modulating alveolar macrophage antiviral immunity," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Dingxi Zhou & Mariana Borsa & Daniel J. Puleston & Susanne Zellner & Jesusa Capera & Sharon Sanderson & Martina Schifferer & Svenja S. Hester & Xin Ge & Roman Fischer & Luke Jostins & Christian Behren, 2022. "Mapping autophagosome contents identifies interleukin-7 receptor-α as a key cargo modulating CD4+ T cell proliferation," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33882-w. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.