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Loss of vascular endothelial notch signaling promotes spontaneous formation of tertiary lymphoid structures
Tertiary lymphoid structures (TLS) are lymph node-like immune cell clusters that emerge during chronic inflammation in non-lymphoid organs like the kidney, but their origin remains not well understood. Here we show, using conditional deletion strategies of the canonical Notch signaling mediator Rbpj...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9018798/ https://www.ncbi.nlm.nih.gov/pubmed/35440634 http://dx.doi.org/10.1038/s41467-022-29701-x |
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author | Fleig, Susanne Kapanadze, Tamar Bernier-Latmani, Jeremiah Lill, Julia K. Wyss, Tania Gamrekelashvili, Jaba Kijas, Dustin Liu, Bin Hüsing, Anne M. Bovay, Esther Jirmo, Adan Chari Halle, Stephan Ricke-Hoch, Melanie Adams, Ralf H. Engel, Daniel R. von Vietinghoff, Sibylle Förster, Reinhold Hilfiker-Kleiner, Denise Haller, Hermann Petrova, Tatiana V. Limbourg, Florian P. |
author_facet | Fleig, Susanne Kapanadze, Tamar Bernier-Latmani, Jeremiah Lill, Julia K. Wyss, Tania Gamrekelashvili, Jaba Kijas, Dustin Liu, Bin Hüsing, Anne M. Bovay, Esther Jirmo, Adan Chari Halle, Stephan Ricke-Hoch, Melanie Adams, Ralf H. Engel, Daniel R. von Vietinghoff, Sibylle Förster, Reinhold Hilfiker-Kleiner, Denise Haller, Hermann Petrova, Tatiana V. Limbourg, Florian P. |
author_sort | Fleig, Susanne |
collection | PubMed |
description | Tertiary lymphoid structures (TLS) are lymph node-like immune cell clusters that emerge during chronic inflammation in non-lymphoid organs like the kidney, but their origin remains not well understood. Here we show, using conditional deletion strategies of the canonical Notch signaling mediator Rbpj, that loss of endothelial Notch signaling in adult mice induces the spontaneous formation of bona fide TLS in the kidney, liver and lung, based on molecular, cellular and structural criteria. These TLS form in a stereotypical manner around parenchymal arteries, while secondary lymphoid structures remained largely unchanged. This effect is mediated by endothelium of blood vessels, but not lymphatics, since a lymphatic endothelial-specific targeting strategy did not result in TLS formation, and involves loss of arterial specification and concomitant acquisition of a high endothelial cell phenotype, as shown by transcriptional analysis of kidney endothelial cells. This indicates a so far unrecognized role for vascular endothelial cells and Notch signaling in TLS initiation. |
format | Online Article Text |
id | pubmed-9018798 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-90187982022-04-28 Loss of vascular endothelial notch signaling promotes spontaneous formation of tertiary lymphoid structures Fleig, Susanne Kapanadze, Tamar Bernier-Latmani, Jeremiah Lill, Julia K. Wyss, Tania Gamrekelashvili, Jaba Kijas, Dustin Liu, Bin Hüsing, Anne M. Bovay, Esther Jirmo, Adan Chari Halle, Stephan Ricke-Hoch, Melanie Adams, Ralf H. Engel, Daniel R. von Vietinghoff, Sibylle Förster, Reinhold Hilfiker-Kleiner, Denise Haller, Hermann Petrova, Tatiana V. Limbourg, Florian P. Nat Commun Article Tertiary lymphoid structures (TLS) are lymph node-like immune cell clusters that emerge during chronic inflammation in non-lymphoid organs like the kidney, but their origin remains not well understood. Here we show, using conditional deletion strategies of the canonical Notch signaling mediator Rbpj, that loss of endothelial Notch signaling in adult mice induces the spontaneous formation of bona fide TLS in the kidney, liver and lung, based on molecular, cellular and structural criteria. These TLS form in a stereotypical manner around parenchymal arteries, while secondary lymphoid structures remained largely unchanged. This effect is mediated by endothelium of blood vessels, but not lymphatics, since a lymphatic endothelial-specific targeting strategy did not result in TLS formation, and involves loss of arterial specification and concomitant acquisition of a high endothelial cell phenotype, as shown by transcriptional analysis of kidney endothelial cells. This indicates a so far unrecognized role for vascular endothelial cells and Notch signaling in TLS initiation. Nature Publishing Group UK 2022-04-19 /pmc/articles/PMC9018798/ /pubmed/35440634 http://dx.doi.org/10.1038/s41467-022-29701-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Fleig, Susanne Kapanadze, Tamar Bernier-Latmani, Jeremiah Lill, Julia K. Wyss, Tania Gamrekelashvili, Jaba Kijas, Dustin Liu, Bin Hüsing, Anne M. Bovay, Esther Jirmo, Adan Chari Halle, Stephan Ricke-Hoch, Melanie Adams, Ralf H. Engel, Daniel R. von Vietinghoff, Sibylle Förster, Reinhold Hilfiker-Kleiner, Denise Haller, Hermann Petrova, Tatiana V. Limbourg, Florian P. Loss of vascular endothelial notch signaling promotes spontaneous formation of tertiary lymphoid structures |
title | Loss of vascular endothelial notch signaling promotes spontaneous formation of tertiary lymphoid structures |
title_full | Loss of vascular endothelial notch signaling promotes spontaneous formation of tertiary lymphoid structures |
title_fullStr | Loss of vascular endothelial notch signaling promotes spontaneous formation of tertiary lymphoid structures |
title_full_unstemmed | Loss of vascular endothelial notch signaling promotes spontaneous formation of tertiary lymphoid structures |
title_short | Loss of vascular endothelial notch signaling promotes spontaneous formation of tertiary lymphoid structures |
title_sort | loss of vascular endothelial notch signaling promotes spontaneous formation of tertiary lymphoid structures |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9018798/ https://www.ncbi.nlm.nih.gov/pubmed/35440634 http://dx.doi.org/10.1038/s41467-022-29701-x |
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