Airway Epithelial Cells Regulate the Functional Phenotype of Locally Differentiating Dendritic Cells: Implications for the Pathogenesis of Infectious and Allergic Airway Disease
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Atopic asthma pathogenesis is driven by the combined effects of airway inflammation generated during responses to viral infections and aeroallergens, and both these pathways are regulated by dendritic cells (DC) that differentiate locally from monocytic precursors. These DCs normally exhibit a sentinel phenotype characterized by active Ag sampling but attenuated presentation capability, which limits the intensity of local expression of adaptive immunity. How this tight control of airway DC functions is normally maintained, and why it breaks down in some atopics leading to immunopathological changes in airway tissues, is unknown. We postulated that signals from adjacent airway epithelial cells (AEC) contribute to regulation of local differentiation of DC. We tested this in a coculture model containing both cell types in a GM-CSF-IL-4-enriched cytokine milieu characteristic of the atopic asthmatic airway mucosa. We demonstrate that contact with AEC during DC differentiation up-regulates expression of the function-associated markers MHC class II, CD40, CD80, TLR3, and TLR4 on DCs with concomitant up-regulation of Ag uptake/processing. Moreover, the AEC-conditioned DCs displayed increased LPS responsiveness evidenced by higher production of IL-12, IL-6, IL-10, and TNF-α. The Th2 memory-activating properties of AEC-conditioned DCs were also selectively attenuated. Data from microarray and blocking experiments implicate AEC-derived type 1 IFNs and IL-6 in modulation of DC differentiation. Collectively, these findings suggest that resting AECs modulate local DC differentiation to optimize antimicrobial defenses in the airways and in the process down-modulate capacity for expression of potentially damaging Th2 immunity.
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Airway epithelial cells are increasingly recognized as important players in processes driving local cDC differentiation and maturation via production of various cytokines, including IL-15, TSLP, and type I IFNs.
“Airway epithelial cells are increasingly recognized as important players in the processes driving local cDC differentiation and maturation via production of various cytokines, including IL-15, thymic stromal lymphopoietin (TSLP), and type I IFNs (227, 230, 272, 289).”
From The airway epithelium: soldier in the fight against respiratory viruses (2011) · cites this paper as [230]
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The airway epithelium: soldier in the fight against respiratory viruses
Vareille, M., Kieninger, E., Edwards, M. R., & Regamey, N. (2011) · Clinical Microbiology Reviews · doi:10.1128/cmr.00014-10 · Cited by 655 · see citing works
Innate immune responses of airway epithelial cells to infection with Equine herpesvirus-1
Soboll Hussey, G., Ashton, L. V., Quintana, A. M., Lunn, D. P., Goehring, L. S., Annis, K., & Landolt, G. (2014) · Veterinary Microbiology · doi:10.1016/j.vetmic.2014.01.018 · Cited by 37 · see citing works
Equine herpesvirus type 1 pUL56 modulates innate responses of airway epithelial cells.
Soboll Hussey, G., Ashton, L. V., Quintana, A. M., Van de Walle, G. R., Osterrieder, N., & Lunn, D. P. (2014) · Virology · doi:10.1016/j.virol.2014.05.023 · Cited by 28 · see citing works
- Authors
- Rate, A., Upham, J. W., Bosco, A., McKenna, K. L., & Holt, P. G.
- Affiliations
- The Kids Research Institute Australia (AU)
- The University of Queensland (AU)
- Corresponding author
- Rate, Angela
- Bosco, Anthony
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-01-01
- Volume
- 182
- Issue
- 1
- Pages
- 72-83
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1495158135
- Cited by
- 88
- References
- 96
- Citations by year
- 2024: 2 · 2023: 1 · 2022: 3 · 2021: 2 · 2020: 2 · 2019: 1 · 2018: 3 · 2017: 4 · 2016: 4 · 2015: 11 · 2014: 6 · 2013: 4 · 2012: 11
- FWCI
- 9.72
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- Funders
- Medical Research Council
- National Health and Medical Research Council
- Topics
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Immunology and Allergy › Allergic Rhinitis and Sensitization
- Keywords
- airway epithelial cells, dendritic cell differentiation, allergic asthma, airway inflammation, MHC class II, TLR3, TLR4, CD40, CD80, LPS responsiveness, Th2 immune response, type I interferon, interleukin-6, GM-CSF, IL-4, allergic airway disease, viral infection
- MeSH terms
- Adult, Aged, Bronchi, Cell Differentiation, Cell Line, Transformed, Cells, Cultured, Dendritic Cells, Humans, Hypersensitivity, Immunologic Memory, Lung, Lymphocyte Activation, Middle Aged, Monocytes, Virus Diseases, Immunophenotyping, T-Lymphocyte Subsets, Cytokines, Coculture Techniques, Lipopolysaccharide Receptors, Respiratory Mucosa, Gene Expression Profiling
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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