Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2015 Apr;45(4):1150-62.
doi: 10.1183/09031936.00141514. Epub 2015 Feb 19.

The innate immune function of airway epithelial cells in inflammatory lung disease

Pieter S Hiemstra  1 , Paul B McCray Jr  2 , Robert Bals  3
Affiliations
Review

The innate immune function of airway epithelial cells in inflammatory lung disease

Pieter S Hiemstra et al. Eur Respir J. 2015 Apr.

Abstract

The airway epithelium is now considered to be central to the orchestration of pulmonary inflammatory and immune responses, and is also key to tissue remodelling. It acts as the first barrier in the defence against a wide range of inhaled challenges, and is critically involved in the regulation of both innate and adaptive immune responses to these challenges. Recent progress in our understanding of the developmental regulation of this tissue, the differentiation pathways, recognition of pathogens and antimicrobial responses is now exploited to help understand how epithelial cell function and dysfunction contributes to the pathogenesis of a variety of inflammatory lung diseases. Herein, advances in our knowledge of the biology of airway epithelium, as well as its role and (dys)function in asthma, chronic obstructive pulmonary fibrosis and cystic fibrosis will be discussed.

PubMed Disclaimer

Figures

Figure 1
Figure 1. The innate immune function of the airway epithelium: sensing microbial presence and antimicrobial effector mechanisms
Various cell types are involved in the innate immune function of the airway epithelium, including the basal cells, goblet cells, ciliated cells and club cells. Microbial presence is detected by pattern recognition receptors (PRR): membrane-bound Toll-like receptors (TLR) and C-type lectin receptors (CLR), and cytoplasmic RIG-I-like receptors (RLR) and NOD-like receptors (NLR). Also other mechanisms are involved in this recognition process, including endoplasmic reticulum (ER) stress and the integrated stress response (ISR). Antimicrobial effector mechanisms include the barrier function of the epithelium, mucociliairy clearance and the antimicrobial activity of mucus, antimicrobial peptides, reactive oxygen species (ROS) and reactive nitrogen species (RNS), antiviral interferons (type I and III interferons) and autophagy. In addition, production of cytokines, chemokines and other mediators results in the recruitment of cells of the adaptive and innate immune system that may contribute to host defence.
Figure 2
Figure 2. Airway epithelial dysfunction in asthma, COPD and cystic fibrosis
Several mechanisms related to the innate immune function of AEC are altered or dysfunctional in asthma, COPD and cystic fibrosis.
See this image and copyright information in PMC

References

    1. Bals R, Hiemstra PS. Innate immunity in the lung: how epithelial cells fight against respiratory pathogens. Eur Respir J. 2004 Feb;23(2):327–33. - PubMed
    1. Parker D, Prince A. Innate Immunity in the Respiratory Epithelium. Am J Respir Cell Mol Biol. 2011 Aug 1;45(2):189–201. - PMC - PubMed
    1. Li Y, Eggermont K, Vanslembrouck V, Verfaillie CM. NKX2–1 activation by SMAD2 signaling after definitive endoderm differentiation in human embryonic stem cell. Stem Cells Dev. 2013 May 1;22(9):1433–42. - PMC - PubMed
    1. Wong AP, Bear CE, Chin S, Pasceri P, Thompson TO, Huan LJ, et al. Directed differentiation of human pluripotent stem cells into mature airway epithelia expressing functional CFTR protein. Nat Biotechnol. 2012 Sep;30(9):876–82. - PMC - PubMed
    1. Firth AL, Dargitz CT, Qualls SJ, Menon T, Wright R, Singer O, et al. Generation of multiciliated cells in functional airway epithelia from human induced pluripotent stem cells. Proc Natl Acad Sci U S A. 2014 Apr 29;111(17):E1723–E1730. - PMC - PubMed

Publication types