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Upregulated expression of Notch1/4 - JAG-1/DLL-1 detected in allergic rhinitis
BACKGROUND: Allergic rhinitis (AR) is a chronic disease with high prevalence. There are currently many treatments available. However, despite an often good therapeutic response, many patients still report impairment in quality of life (QoL) during the pollen season. A skewed T helper (Th)2 polarizat...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10183115/ https://www.ncbi.nlm.nih.gov/pubmed/37183251 http://dx.doi.org/10.1186/s13223-023-00793-4 |
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author | Hjalmarsson, Eric Petro, Marianne Georén, Susanna Kumlien Winqvist, Ola Cardell, Lars Olaf |
author_facet | Hjalmarsson, Eric Petro, Marianne Georén, Susanna Kumlien Winqvist, Ola Cardell, Lars Olaf |
author_sort | Hjalmarsson, Eric |
collection | PubMed |
description | BACKGROUND: Allergic rhinitis (AR) is a chronic disease with high prevalence. There are currently many treatments available. However, despite an often good therapeutic response, many patients still report impairment in quality of life (QoL) during the pollen season. A skewed T helper (Th)2 polarization is a well-acknowledged pathologic feature of AR. In animal models, local notch signaling in peripheral tissue seems crucial for Th2 cell differentiation and the development of AR. However, the involvement of Notch signaling in Th2 cell differentiation and the development of AR in humans remains unknown. Hence, the present study investigated the human expression of Notch receptors on CD4(+) T-cells in nasal mucosa and blood. Correspondingly Notch ligand expression was assessed on nasal epithelial cells and neutrophils. METHODOLOGY: Nasal brush and blood samples from 18 patients with pollen-induced AR and 22 healthy controls were collected outside the pollen season. Notch 1–4 and Jagged-1,2 and Delta-like ligand 1,3–4 was analyzed using flow cytometry. RESULTS: The fraction of CD4(+)Notch1(+) and CD4(+)Notch4(+) T-cells was higher in AR patients than in healthy control patients. Further, the expression levels of the Notch ligands JAG-1 and DLL-1 were increased in nasal epithelial cells from AR patients compared to healthy control patients. In addition, AR patients displayed higher expression of JAG-1 on neutrophils both in the nasal mucosa and in peripheral blood. CONCLUSION: The present study is the first to demonstrate increased activity in the Notch1/4 - JAG-1/DLL-1 pathways among allergic individuals. Further propagating the importance of Notch signalling in AR and blocking JAG-1 and DLL-1-induced Notch signalling by nasal epithelial cells and Neutrophils are potential targets to reduce allergic airway inflammation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13223-023-00793-4. |
format | Online Article Text |
id | pubmed-10183115 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-101831152023-05-15 Upregulated expression of Notch1/4 - JAG-1/DLL-1 detected in allergic rhinitis Hjalmarsson, Eric Petro, Marianne Georén, Susanna Kumlien Winqvist, Ola Cardell, Lars Olaf Allergy Asthma Clin Immunol Research BACKGROUND: Allergic rhinitis (AR) is a chronic disease with high prevalence. There are currently many treatments available. However, despite an often good therapeutic response, many patients still report impairment in quality of life (QoL) during the pollen season. A skewed T helper (Th)2 polarization is a well-acknowledged pathologic feature of AR. In animal models, local notch signaling in peripheral tissue seems crucial for Th2 cell differentiation and the development of AR. However, the involvement of Notch signaling in Th2 cell differentiation and the development of AR in humans remains unknown. Hence, the present study investigated the human expression of Notch receptors on CD4(+) T-cells in nasal mucosa and blood. Correspondingly Notch ligand expression was assessed on nasal epithelial cells and neutrophils. METHODOLOGY: Nasal brush and blood samples from 18 patients with pollen-induced AR and 22 healthy controls were collected outside the pollen season. Notch 1–4 and Jagged-1,2 and Delta-like ligand 1,3–4 was analyzed using flow cytometry. RESULTS: The fraction of CD4(+)Notch1(+) and CD4(+)Notch4(+) T-cells was higher in AR patients than in healthy control patients. Further, the expression levels of the Notch ligands JAG-1 and DLL-1 were increased in nasal epithelial cells from AR patients compared to healthy control patients. In addition, AR patients displayed higher expression of JAG-1 on neutrophils both in the nasal mucosa and in peripheral blood. CONCLUSION: The present study is the first to demonstrate increased activity in the Notch1/4 - JAG-1/DLL-1 pathways among allergic individuals. Further propagating the importance of Notch signalling in AR and blocking JAG-1 and DLL-1-induced Notch signalling by nasal epithelial cells and Neutrophils are potential targets to reduce allergic airway inflammation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13223-023-00793-4. BioMed Central 2023-05-14 /pmc/articles/PMC10183115/ /pubmed/37183251 http://dx.doi.org/10.1186/s13223-023-00793-4 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Hjalmarsson, Eric Petro, Marianne Georén, Susanna Kumlien Winqvist, Ola Cardell, Lars Olaf Upregulated expression of Notch1/4 - JAG-1/DLL-1 detected in allergic rhinitis |
title | Upregulated expression of Notch1/4 - JAG-1/DLL-1 detected in allergic rhinitis |
title_full | Upregulated expression of Notch1/4 - JAG-1/DLL-1 detected in allergic rhinitis |
title_fullStr | Upregulated expression of Notch1/4 - JAG-1/DLL-1 detected in allergic rhinitis |
title_full_unstemmed | Upregulated expression of Notch1/4 - JAG-1/DLL-1 detected in allergic rhinitis |
title_short | Upregulated expression of Notch1/4 - JAG-1/DLL-1 detected in allergic rhinitis |
title_sort | upregulated expression of notch1/4 - jag-1/dll-1 detected in allergic rhinitis |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10183115/ https://www.ncbi.nlm.nih.gov/pubmed/37183251 http://dx.doi.org/10.1186/s13223-023-00793-4 |
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