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IL-1 and TNFα Contribute to the Inflammatory Niche to Enhance Alveolar Regeneration
Inflammatory responses are known to facilitate tissue recovery following injury. However, the precise mechanisms that enhance lung alveolar regeneration remain unclear. Here, using an organoid-based screening assay, we find that interleukin-1 (IL-1) and tumor necrosis factor α (TNFα) enhance the pro...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6450459/ https://www.ncbi.nlm.nih.gov/pubmed/30930244 http://dx.doi.org/10.1016/j.stemcr.2019.02.013 |
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author | Katsura, Hiroaki Kobayashi, Yoshihiko Tata, Purushothama Rao Hogan, Brigid L.M. |
author_facet | Katsura, Hiroaki Kobayashi, Yoshihiko Tata, Purushothama Rao Hogan, Brigid L.M. |
author_sort | Katsura, Hiroaki |
collection | PubMed |
description | Inflammatory responses are known to facilitate tissue recovery following injury. However, the precise mechanisms that enhance lung alveolar regeneration remain unclear. Here, using an organoid-based screening assay, we find that interleukin-1 (IL-1) and tumor necrosis factor α (TNFα) enhance the proliferation of AEC2s while maintaining their differentiation capacity. Furthermore, we find that expression of IL-1β and TNFα are induced in the AEC2 niche following influenza-induced injury in vivo, and lineage tracing analysis revealed that surviving AEC2s around the damaged area contribute to alveolar regeneration. Through genetic and pharmacological modulation of multiple components of the IL-1-nuclear factor κB (NF-κB) signaling axis, we show that cell-intrinsic as well as stromal mediated IL-1 signaling are essential for AEC2 mediated lung regeneration. Taken together, we propose that the IL-1/TNFα-NF-κB signaling axis functions as a component of an inflammation-associated niche to regulate proliferation of surviving AEC2s and promote lung regeneration. |
format | Online Article Text |
id | pubmed-6450459 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-64504592019-04-16 IL-1 and TNFα Contribute to the Inflammatory Niche to Enhance Alveolar Regeneration Katsura, Hiroaki Kobayashi, Yoshihiko Tata, Purushothama Rao Hogan, Brigid L.M. Stem Cell Reports Report Inflammatory responses are known to facilitate tissue recovery following injury. However, the precise mechanisms that enhance lung alveolar regeneration remain unclear. Here, using an organoid-based screening assay, we find that interleukin-1 (IL-1) and tumor necrosis factor α (TNFα) enhance the proliferation of AEC2s while maintaining their differentiation capacity. Furthermore, we find that expression of IL-1β and TNFα are induced in the AEC2 niche following influenza-induced injury in vivo, and lineage tracing analysis revealed that surviving AEC2s around the damaged area contribute to alveolar regeneration. Through genetic and pharmacological modulation of multiple components of the IL-1-nuclear factor κB (NF-κB) signaling axis, we show that cell-intrinsic as well as stromal mediated IL-1 signaling are essential for AEC2 mediated lung regeneration. Taken together, we propose that the IL-1/TNFα-NF-κB signaling axis functions as a component of an inflammation-associated niche to regulate proliferation of surviving AEC2s and promote lung regeneration. Elsevier 2019-03-28 /pmc/articles/PMC6450459/ /pubmed/30930244 http://dx.doi.org/10.1016/j.stemcr.2019.02.013 Text en © 2019 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Report Katsura, Hiroaki Kobayashi, Yoshihiko Tata, Purushothama Rao Hogan, Brigid L.M. IL-1 and TNFα Contribute to the Inflammatory Niche to Enhance Alveolar Regeneration |
title | IL-1 and TNFα Contribute to the Inflammatory Niche to Enhance Alveolar Regeneration |
title_full | IL-1 and TNFα Contribute to the Inflammatory Niche to Enhance Alveolar Regeneration |
title_fullStr | IL-1 and TNFα Contribute to the Inflammatory Niche to Enhance Alveolar Regeneration |
title_full_unstemmed | IL-1 and TNFα Contribute to the Inflammatory Niche to Enhance Alveolar Regeneration |
title_short | IL-1 and TNFα Contribute to the Inflammatory Niche to Enhance Alveolar Regeneration |
title_sort | il-1 and tnfα contribute to the inflammatory niche to enhance alveolar regeneration |
topic | Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6450459/ https://www.ncbi.nlm.nih.gov/pubmed/30930244 http://dx.doi.org/10.1016/j.stemcr.2019.02.013 |
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