Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Correspondence
  • Published:

‘Bedside’ observations challenge aspects of the ‘epithelial barrier hypothesis’

Nature Reviews Immunology volume 21, page 829 (2021)Cite this article

Subjects

Access through your institution
Buy or subscribe

In his Review, Akdis explains the rise in prevalence of allergic and chronic inflammatory diseases by proposing that ‘leaky epithelial barriers’ caused by environmental toxins lead to colonization by opportunistic pathogens and to microbial dysbiosis, and that immune responses to pathogens promote further barrier defects in a vicious circle (Akdis, C. A. Does the epithelial barrier hypothesis explain the increase in allergy, autoimmunity and other chronic conditions? Nat. Rev. Immunol. https://doi.org/10.1038/s41577-021-00538-7 (2021))1. However, ‘bedside’ data in patients with asthma and allergic rhinitis argue against the idea of a leaky epithelial barrier in these conditions. The common expression ‘leaky epithelial barrier’ actually eclipses an important asymmetry of the barrier functions of human conducting airways.

The popular notion that increased nasal absorption of allergens occurs in individuals who are atopic was first tested in 1930. Contrary to expectations, decreased ‘absorption’ was observed2. With novel methods that control for potential confounding factors (mucosal surface concentration of absorption tracer, influence of mucociliary clearance, area of exposed airway mucosa and time of exposure), similar results were found in individuals suffering from perennial allergic rhinitis3 and especially in active seasonal allergic rhinitis when, paradoxically, the outward penetrability of the nasal mucosal membrane to non-sieved plasma macromolecules was much increased4,5.

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Akdis, C. A. Does the epithelial barrier hypothesis explain the increase in allergy, autoimmunity and other chronic conditions? Nat. Rev. Immunol. https://doi.org/10.1038/s41577-021-00538-7 (2021).

    Article  PubMed  Google Scholar 

  2. Cohen, M. B. et al. The rate of absorption of ragweed pollen material from the nose. J. Immunol. 18, 419–425 (1930).

    Google Scholar 

  3. Greiff, L. et al. Absorption across the nasal airway mucosa in house dust mite perennial allergic rhinitis. Clin. Physiol. Funct. Imaging 22, 55–57 (2002).

    Article  Google Scholar 

  4. Greiff, L. et al. Reduced airway absorption in seasonal allergic rhinitis. Am. J. Respir. Crit. Care Med. 156, 783–786 (1997).

    Article  CAS  Google Scholar 

  5. Persson, C. Airways exudation of plasma macromolecules: Innate defense, epithelial regeneration, and asthma. J. Allergy Clin. Immunol. 143, 1271–1286 (2019).

    Article  CAS  Google Scholar 

  6. Persson, C. Early humoral defence: Contributing to confining COVID-19 to conducting airways? Scand. J. Immunol. https://doi.org/10.1111/sji.13024 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  7. O’Byrne, P. M. et al. Lung epithelial permeability: relation to non-specific airway responsiveness. J. Appl. Physiol. Respir. Environ. Exerc. Physiol. 57, 77–84 (1984).

    PubMed  Google Scholar 

  8. Del Donno, M. et al. Lung epithelial permeability and bronchial responsiveness in subjects with stable asthma. Chest 111, 1255–1260 (1997).

    Article  Google Scholar 

  9. Georas, S. et al. The leaky lung test: A pilot study using inhaled mannitol to measure airway barrier function in asthma. J. Asthma 56, 1257–1265 (2019).

    Article  CAS  Google Scholar 

  10. Persson, C. Humoral first-line mucosal innate defence in vivo. J. Innate Immun. 12, 373–386 (2020).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Laboratory Medicine, University Hospital of Lund, Lund, Sweden

    Carl Persson

Authors
  1. Carl Persson
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to Carl Persson.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Persson, C. ‘Bedside’ observations challenge aspects of the ‘epithelial barrier hypothesis’. Nat Rev Immunol 21, 829 (2021). https://doi.org/10.1038/s41577-021-00650-8

Download citation

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41577-021-00650-8

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing