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Pulmonary immune cell transcriptome changes in double-hit model of BPD induced by chorioamnionitis and postnatal hyperoxia
BACKGROUND: Preterm infants with bronchopulmonary dysplasia (BPD) have lifelong increased risk of respiratory morbidities associated with environmental pathogen exposure and underlying mechanisms are poorly understood. The resident immune cells of the lung play vital roles in host defense. However,...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group US
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808307/ https://www.ncbi.nlm.nih.gov/pubmed/33446917 http://dx.doi.org/10.1038/s41390-020-01319-z |
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author | Shrestha, Diksha Ye, George Xiangyun Stabley, Deborah Betal, Suhita Gayen nee’ Zhu, Yan Glazewski, Lisa Holbrook, Jennifer Sethi, Meharpreet Hesek, Anne Shaffer, Thomas H. Aghai, Zubair H. Addya, Sankar Alapati, Deepthi |
author_facet | Shrestha, Diksha Ye, George Xiangyun Stabley, Deborah Betal, Suhita Gayen nee’ Zhu, Yan Glazewski, Lisa Holbrook, Jennifer Sethi, Meharpreet Hesek, Anne Shaffer, Thomas H. Aghai, Zubair H. Addya, Sankar Alapati, Deepthi |
author_sort | Shrestha, Diksha |
collection | PubMed |
description | BACKGROUND: Preterm infants with bronchopulmonary dysplasia (BPD) have lifelong increased risk of respiratory morbidities associated with environmental pathogen exposure and underlying mechanisms are poorly understood. The resident immune cells of the lung play vital roles in host defense. However, the effect of perinatal events associated with BPD on pulmonary-specific immune cells is not well understood. METHODS: We used a double-hit model of BPD induced by prenatal chorioamnionitis followed by postnatal hyperoxia, and performed a global transcriptome analysis of all resident pulmonary immune cells. RESULTS: We show significant up-regulation of genes involved in chemokine-mediated signaling and immune cell chemotaxis, and down-regulation of genes involved in multiple T lymphocyte functions. Multiple genes involved in T cell receptor signaling are downregulated and Cd8a gene expression remains downregulated at 2 months of age in spite of recovery in normoxia for 6 weeks. Furthermore, the proportion of CD8a+CD3+ pulmonary immune cells is decreased. CONCLUSIONS: Our study has highlighted that perinatal lung inflammation in a double-hit model of BPD results in short- and long-term dysregulation of genes associated with the pulmonary T cell receptor signaling pathway, which may contribute to increased environmental pathogen-associated respiratory morbidities seen in children and adults with BPD. IMPACT: In a translationally relevant double-hit model of BPD induced by chorioamnionitis and postnatal hyperoxia, we identified pulmonary immune cell-specific transcriptomic changes and showed that T cell receptor signaling genes are downregulated in short term and long term. This is the first comprehensive report delineating transcriptomic changes in resident immune cells of the lung in a translationally relevant double-hit model of BPD. Our study identifies novel resident pulmonary immune cell-specific targets for potential therapeutic modulation to improve short- and long-term respiratory health of preterm infants with BPD. |
format | Online Article Text |
id | pubmed-7808307 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group US |
record_format | MEDLINE/PubMed |
spelling | pubmed-78083072021-01-15 Pulmonary immune cell transcriptome changes in double-hit model of BPD induced by chorioamnionitis and postnatal hyperoxia Shrestha, Diksha Ye, George Xiangyun Stabley, Deborah Betal, Suhita Gayen nee’ Zhu, Yan Glazewski, Lisa Holbrook, Jennifer Sethi, Meharpreet Hesek, Anne Shaffer, Thomas H. Aghai, Zubair H. Addya, Sankar Alapati, Deepthi Pediatr Res Basic Science Article BACKGROUND: Preterm infants with bronchopulmonary dysplasia (BPD) have lifelong increased risk of respiratory morbidities associated with environmental pathogen exposure and underlying mechanisms are poorly understood. The resident immune cells of the lung play vital roles in host defense. However, the effect of perinatal events associated with BPD on pulmonary-specific immune cells is not well understood. METHODS: We used a double-hit model of BPD induced by prenatal chorioamnionitis followed by postnatal hyperoxia, and performed a global transcriptome analysis of all resident pulmonary immune cells. RESULTS: We show significant up-regulation of genes involved in chemokine-mediated signaling and immune cell chemotaxis, and down-regulation of genes involved in multiple T lymphocyte functions. Multiple genes involved in T cell receptor signaling are downregulated and Cd8a gene expression remains downregulated at 2 months of age in spite of recovery in normoxia for 6 weeks. Furthermore, the proportion of CD8a+CD3+ pulmonary immune cells is decreased. CONCLUSIONS: Our study has highlighted that perinatal lung inflammation in a double-hit model of BPD results in short- and long-term dysregulation of genes associated with the pulmonary T cell receptor signaling pathway, which may contribute to increased environmental pathogen-associated respiratory morbidities seen in children and adults with BPD. IMPACT: In a translationally relevant double-hit model of BPD induced by chorioamnionitis and postnatal hyperoxia, we identified pulmonary immune cell-specific transcriptomic changes and showed that T cell receptor signaling genes are downregulated in short term and long term. This is the first comprehensive report delineating transcriptomic changes in resident immune cells of the lung in a translationally relevant double-hit model of BPD. Our study identifies novel resident pulmonary immune cell-specific targets for potential therapeutic modulation to improve short- and long-term respiratory health of preterm infants with BPD. Nature Publishing Group US 2021-01-14 2021 /pmc/articles/PMC7808307/ /pubmed/33446917 http://dx.doi.org/10.1038/s41390-020-01319-z Text en © The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc 2021 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic. |
spellingShingle | Basic Science Article Shrestha, Diksha Ye, George Xiangyun Stabley, Deborah Betal, Suhita Gayen nee’ Zhu, Yan Glazewski, Lisa Holbrook, Jennifer Sethi, Meharpreet Hesek, Anne Shaffer, Thomas H. Aghai, Zubair H. Addya, Sankar Alapati, Deepthi Pulmonary immune cell transcriptome changes in double-hit model of BPD induced by chorioamnionitis and postnatal hyperoxia |
title | Pulmonary immune cell transcriptome changes in double-hit model of BPD induced by chorioamnionitis and postnatal hyperoxia |
title_full | Pulmonary immune cell transcriptome changes in double-hit model of BPD induced by chorioamnionitis and postnatal hyperoxia |
title_fullStr | Pulmonary immune cell transcriptome changes in double-hit model of BPD induced by chorioamnionitis and postnatal hyperoxia |
title_full_unstemmed | Pulmonary immune cell transcriptome changes in double-hit model of BPD induced by chorioamnionitis and postnatal hyperoxia |
title_short | Pulmonary immune cell transcriptome changes in double-hit model of BPD induced by chorioamnionitis and postnatal hyperoxia |
title_sort | pulmonary immune cell transcriptome changes in double-hit model of bpd induced by chorioamnionitis and postnatal hyperoxia |
topic | Basic Science Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808307/ https://www.ncbi.nlm.nih.gov/pubmed/33446917 http://dx.doi.org/10.1038/s41390-020-01319-z |
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