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Chronic developmental hypoxia alters rat lung immune cell transcriptomes during allergic airway inflammation

Populations that are born and raised at high altitude develop under conditions of chronic developmental hypoxia (CDH), which results in pulmonary adaptations of increased lung volume and diffusion capacity to increase gas exchange. It is not clear how CDH may alter allergic inflammation in the lung....

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Autores principales: Chu, Michelle, Gao, Huanling, Esparza, Patricia, Pajulas, Abigail, Wang, Jocelyn, Kharwadkar, Rakshin, Gao, Hongyu, Kaplan, Mark H., Tepper, Robert S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9904961/
https://www.ncbi.nlm.nih.gov/pubmed/36750205
http://dx.doi.org/10.14814/phy2.15600
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author Chu, Michelle
Gao, Huanling
Esparza, Patricia
Pajulas, Abigail
Wang, Jocelyn
Kharwadkar, Rakshin
Gao, Hongyu
Kaplan, Mark H.
Tepper, Robert S.
author_facet Chu, Michelle
Gao, Huanling
Esparza, Patricia
Pajulas, Abigail
Wang, Jocelyn
Kharwadkar, Rakshin
Gao, Hongyu
Kaplan, Mark H.
Tepper, Robert S.
author_sort Chu, Michelle
collection PubMed
description Populations that are born and raised at high altitude develop under conditions of chronic developmental hypoxia (CDH), which results in pulmonary adaptations of increased lung volume and diffusion capacity to increase gas exchange. It is not clear how CDH may alter allergic inflammation in the lung. In this study, we sought to characterize the impact of CDH on immune cell populations in the rat lung during a murine model of asthma. Rats were bred and raised in either hypoxic (15% oxygen, CDH) or normobaric room air (20% oxygen). At 3‐weeks of age, animals were sensitized to ovalbumin (OVA) or physiologic saline (phosphate‐buffered saline [PBS]) as a control, followed by three consecutive days of intra‐nasal OVA or PBS at 6‐weeks of age. We then assessed airway reactivity and allergic‐associated cytokine levels. This was followed by single‐cell transcriptomic profiling of lung cell populations. In scRNA‐seq analysis, we assessed differentially expressed genes, differentially enriched functional pathways, immune cell exhaustion/activation markers, and immune cell secretory products. Our results show that while OVA heightened airway reactivity, CDH suppressed airway reactivity in OVA‐challenged and control animals. Through scRNA‐seq analysis, we further demonstrate that CDH alters the transcriptional landscape in the lung and alters transcriptional programs in immune cells. These data define CDH‐dependent changes in the lung that impact airway reactivity.
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spelling pubmed-99049612023-02-09 Chronic developmental hypoxia alters rat lung immune cell transcriptomes during allergic airway inflammation Chu, Michelle Gao, Huanling Esparza, Patricia Pajulas, Abigail Wang, Jocelyn Kharwadkar, Rakshin Gao, Hongyu Kaplan, Mark H. Tepper, Robert S. Physiol Rep Original Articles Populations that are born and raised at high altitude develop under conditions of chronic developmental hypoxia (CDH), which results in pulmonary adaptations of increased lung volume and diffusion capacity to increase gas exchange. It is not clear how CDH may alter allergic inflammation in the lung. In this study, we sought to characterize the impact of CDH on immune cell populations in the rat lung during a murine model of asthma. Rats were bred and raised in either hypoxic (15% oxygen, CDH) or normobaric room air (20% oxygen). At 3‐weeks of age, animals were sensitized to ovalbumin (OVA) or physiologic saline (phosphate‐buffered saline [PBS]) as a control, followed by three consecutive days of intra‐nasal OVA or PBS at 6‐weeks of age. We then assessed airway reactivity and allergic‐associated cytokine levels. This was followed by single‐cell transcriptomic profiling of lung cell populations. In scRNA‐seq analysis, we assessed differentially expressed genes, differentially enriched functional pathways, immune cell exhaustion/activation markers, and immune cell secretory products. Our results show that while OVA heightened airway reactivity, CDH suppressed airway reactivity in OVA‐challenged and control animals. Through scRNA‐seq analysis, we further demonstrate that CDH alters the transcriptional landscape in the lung and alters transcriptional programs in immune cells. These data define CDH‐dependent changes in the lung that impact airway reactivity. John Wiley and Sons Inc. 2023-02-07 /pmc/articles/PMC9904961/ /pubmed/36750205 http://dx.doi.org/10.14814/phy2.15600 Text en © 2023 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Chu, Michelle
Gao, Huanling
Esparza, Patricia
Pajulas, Abigail
Wang, Jocelyn
Kharwadkar, Rakshin
Gao, Hongyu
Kaplan, Mark H.
Tepper, Robert S.
Chronic developmental hypoxia alters rat lung immune cell transcriptomes during allergic airway inflammation
title Chronic developmental hypoxia alters rat lung immune cell transcriptomes during allergic airway inflammation
title_full Chronic developmental hypoxia alters rat lung immune cell transcriptomes during allergic airway inflammation
title_fullStr Chronic developmental hypoxia alters rat lung immune cell transcriptomes during allergic airway inflammation
title_full_unstemmed Chronic developmental hypoxia alters rat lung immune cell transcriptomes during allergic airway inflammation
title_short Chronic developmental hypoxia alters rat lung immune cell transcriptomes during allergic airway inflammation
title_sort chronic developmental hypoxia alters rat lung immune cell transcriptomes during allergic airway inflammation
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9904961/
https://www.ncbi.nlm.nih.gov/pubmed/36750205
http://dx.doi.org/10.14814/phy2.15600
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