FcϵRI-mediated thymic stromal lymphopoietin production by interleukin-4-primed human mast cells
Open accessAbstract
A significant increase of mRNA expression of thymic stromal lymphopoietin (TSLP) has been reported in the bronchial mast cells (MCs) of asthmatic subjects; however, the mechanism underlying the upregulation of TSLP mRNA and protein remains unknown. FcϵRI-mediated activation of human MCs upregulated TSLP mRNA expression by 5.2±2.9-fold, while activation of the MCs using lipopolysaccharide and polyriboinosinic:polyribocytidylic acid failed to upregulate TSLP. Stimulation of MCs with interleukin (IL)-4 alone did not affect the TSLP mRNA expression, while pre-incubation of MCs with IL-4 for 48 h significantly enhanced the FcϵRI-mediated TSLP mRNA expression (by 53.7±15.9-fold; p<0.05) and the amount of TSLP in the cell pellets increased significantly from 23.4±4.3 pg·mL−1 to 121.5±3.7 pg·mL−1(p<0.0001). However, the released TSLP was rapidly degraded by proteases that were released by MCs. We identified the population of cells expressing TSLP in the lungs of 16 asthmatic and 11 control subjects by immunohistochemistry. The percentage of TSLP-positive MCs in the total population of MCs was significantly increased in asthmatic airways (p<0.0001). Thus, MCs are able to store TSLP intracellularly and to produce TSLP following aggregation of FcϵRI in the presence of IL-4.
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TSLP activates dendritic cells, promotes Th2 responses, and activates mast cells.
“Further, TSLP has been shown to activate dendritic cells, promote Th2 responses, and activate mast cells.401”
From International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (2018) · cites this paper as [401]
The background section states that TSLP activates dendritic cells and promotes DC-mediated Th2 responses. The Discussion reports that TSLP stimulates Th2 cytokine production by human mast cells, but specifies that this occurs synergistically with IL-1 and TNF-α; it does not establish unqualified mast-cell activation by TSLP alone. (LLM, conf=0.82)
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- Authors
- Okayama, Y., Okumura, S., Sagara, H., Yuki, K., Sasaki, T., Watanabe, N., Fueki, M., Sugiyama, K., Takeda, K., Fukuda, T., Saito, H., & Ra, C.
- Affiliations
- Nihon University (JP)
- Stanford Medicine (US)
- Institute of Medical Science, The University of Tokyo (JP)
- Juntendo University (JP)
- National Research Institute for Child Health and Development (JP)
- Corresponding author
- Okayama, Y.
- Venue
- European Respiratory Journal
- Publisher
- European Respiratory Society (ERS)
- Published
- 2009-01-22
- Volume
- 34
- Issue
- 2
- Pages
- 425-435
- ISSN
- 0903-1936 (ISSN-L)
- 1399-3003
- OpenAlex
- W2160161426
- Cited by
- 100
- References
- 26
- Citations by year
- 2025: 2 · 2024: 4 · 2023: 6 · 2022: 9 · 2021: 4 · 2020: 2 · 2019: 6 · 2018: 11 · 2017: 3 · 2016: 4 · 2015: 6 · 2014: 6 · 2013: 11 · 2012: 7
- FWCI
- 3.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Respiratory Journal (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Dokkyo Medical University
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Health Sciences › Medicine › Immunology and Allergy › Allergic Rhinitis and Sensitization
- Keywords
- thymic stromal lymphopoietin, mast cells, FcεRI, IL-4, asthma, airway inflammation
- MeSH terms
- Thymic Stromal Lymphopoietin, Adult, Asthma, Bronchi, Female, Humans, Immunohistochemistry, Leukocytes, Mononuclear, Male, Mast Cells, Middle Aged, Interleukin-4, Case-Control Studies, Cytokines, Receptors, IgE, Respiratory Mucosa
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