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An Alternative Dendritic Cell-Induced Murine Model of Asthma Exhibiting a Robust Th2/Th17-Skewed Response
PURPOSE: Simple and reliable animal models of human diseases contribute to the understanding of disease pathogenesis as well as the development of therapeutic interventions. Although several murine models to mimic human asthma have been established, most of them require anesthesia, resulting in vari...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Korean Academy of Asthma, Allergy and Clinical Immunology; The Korean Academy of Pediatric Allergy and Respiratory Disease
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7061158/ https://www.ncbi.nlm.nih.gov/pubmed/32141265 http://dx.doi.org/10.4168/aair.2020.12.3.537 |
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author | Park, Sang Chul Kim, Hongmin Bak, Yeeun Shim, Dahee Kwon, Kee Woong Kim, Chang-Hoon Yoon, Joo-Heon Shin, Sung Jae |
author_facet | Park, Sang Chul Kim, Hongmin Bak, Yeeun Shim, Dahee Kwon, Kee Woong Kim, Chang-Hoon Yoon, Joo-Heon Shin, Sung Jae |
author_sort | Park, Sang Chul |
collection | PubMed |
description | PURPOSE: Simple and reliable animal models of human diseases contribute to the understanding of disease pathogenesis as well as the development of therapeutic interventions. Although several murine models to mimic human asthma have been established, most of them require anesthesia, resulting in variability among test individuals, and do not mimic asthmatic responses accompanied by T-helper (Th) 17 and neutrophils. As dendritic cells (DCs) are known to play an important role in initiating and maintaining asthmatic inflammation, we developed an asthma model via adoptive transfer of allergen-loaded DCs. METHODS: Ovalbumin (OVA)-loaded bone marrow-derived DCs (BMDCs) (OVA-BMDCs) were injected intravenously 3 times into non-anesthetized C57BL/6 mice after intraperitoneal OVA-sensitization. RESULTS: OVA-BMDC-transferred mice developed severe asthmatic immune responses when compared with mice receiving conventional OVA challenge intranasally. Notably, remarkable increases in systemic immunoglobulin (Ig) E and IgG1 responses, Th2/Th17-associated cytokines (interleukin [IL]-5, IL-13 and IL-17), Th2/Th17-skewed T-cell responses, and cellular components, including eosinophils, neutrophils, and goblet cells, were observed in the lungs of OVA-BMDC-transferred mice. Moreover, the asthmatic immune responses and severity of inflammation were correlated with the number of OVA-BMDCs transferred, indicating that the disease severity and asthma type may be adjusted according to the experimental purpose by this method. Furthermore, this model exhibited less variation among the test individuals than the conventional model. In addition, this DCs-based asthma model was partially resistant to steroid treatment. CONCLUSIONS: A reliable murine model of asthma by intravenous (i.v.) transfer of OVA-BMDCs was successfully established without anesthesia. This model more accurately reflects heterogeneous human asthma, exhibiting a robust Th2/Th17-skewed response and eosinophilic/neutrophilic infiltration with good reproducibility and low variation among individuals. This model will be useful for understanding the pathogenesis of asthma and would serve as an alternative tool for immunological studies on the function of DCs, T-cell responses and new drugs. |
format | Online Article Text |
id | pubmed-7061158 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | The Korean Academy of Asthma, Allergy and Clinical Immunology; The Korean Academy of Pediatric Allergy and Respiratory Disease |
record_format | MEDLINE/PubMed |
spelling | pubmed-70611582020-05-01 An Alternative Dendritic Cell-Induced Murine Model of Asthma Exhibiting a Robust Th2/Th17-Skewed Response Park, Sang Chul Kim, Hongmin Bak, Yeeun Shim, Dahee Kwon, Kee Woong Kim, Chang-Hoon Yoon, Joo-Heon Shin, Sung Jae Allergy Asthma Immunol Res Original Article PURPOSE: Simple and reliable animal models of human diseases contribute to the understanding of disease pathogenesis as well as the development of therapeutic interventions. Although several murine models to mimic human asthma have been established, most of them require anesthesia, resulting in variability among test individuals, and do not mimic asthmatic responses accompanied by T-helper (Th) 17 and neutrophils. As dendritic cells (DCs) are known to play an important role in initiating and maintaining asthmatic inflammation, we developed an asthma model via adoptive transfer of allergen-loaded DCs. METHODS: Ovalbumin (OVA)-loaded bone marrow-derived DCs (BMDCs) (OVA-BMDCs) were injected intravenously 3 times into non-anesthetized C57BL/6 mice after intraperitoneal OVA-sensitization. RESULTS: OVA-BMDC-transferred mice developed severe asthmatic immune responses when compared with mice receiving conventional OVA challenge intranasally. Notably, remarkable increases in systemic immunoglobulin (Ig) E and IgG1 responses, Th2/Th17-associated cytokines (interleukin [IL]-5, IL-13 and IL-17), Th2/Th17-skewed T-cell responses, and cellular components, including eosinophils, neutrophils, and goblet cells, were observed in the lungs of OVA-BMDC-transferred mice. Moreover, the asthmatic immune responses and severity of inflammation were correlated with the number of OVA-BMDCs transferred, indicating that the disease severity and asthma type may be adjusted according to the experimental purpose by this method. Furthermore, this model exhibited less variation among the test individuals than the conventional model. In addition, this DCs-based asthma model was partially resistant to steroid treatment. CONCLUSIONS: A reliable murine model of asthma by intravenous (i.v.) transfer of OVA-BMDCs was successfully established without anesthesia. This model more accurately reflects heterogeneous human asthma, exhibiting a robust Th2/Th17-skewed response and eosinophilic/neutrophilic infiltration with good reproducibility and low variation among individuals. This model will be useful for understanding the pathogenesis of asthma and would serve as an alternative tool for immunological studies on the function of DCs, T-cell responses and new drugs. The Korean Academy of Asthma, Allergy and Clinical Immunology; The Korean Academy of Pediatric Allergy and Respiratory Disease 2020-01-22 /pmc/articles/PMC7061158/ /pubmed/32141265 http://dx.doi.org/10.4168/aair.2020.12.3.537 Text en Copyright © 2020 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease https://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Park, Sang Chul Kim, Hongmin Bak, Yeeun Shim, Dahee Kwon, Kee Woong Kim, Chang-Hoon Yoon, Joo-Heon Shin, Sung Jae An Alternative Dendritic Cell-Induced Murine Model of Asthma Exhibiting a Robust Th2/Th17-Skewed Response |
title | An Alternative Dendritic Cell-Induced Murine Model of Asthma Exhibiting a Robust Th2/Th17-Skewed Response |
title_full | An Alternative Dendritic Cell-Induced Murine Model of Asthma Exhibiting a Robust Th2/Th17-Skewed Response |
title_fullStr | An Alternative Dendritic Cell-Induced Murine Model of Asthma Exhibiting a Robust Th2/Th17-Skewed Response |
title_full_unstemmed | An Alternative Dendritic Cell-Induced Murine Model of Asthma Exhibiting a Robust Th2/Th17-Skewed Response |
title_short | An Alternative Dendritic Cell-Induced Murine Model of Asthma Exhibiting a Robust Th2/Th17-Skewed Response |
title_sort | alternative dendritic cell-induced murine model of asthma exhibiting a robust th2/th17-skewed response |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7061158/ https://www.ncbi.nlm.nih.gov/pubmed/32141265 http://dx.doi.org/10.4168/aair.2020.12.3.537 |
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