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Endogenous TNFα orchestrates the trafficking of neutrophils into and within lymphatic vessels during acute inflammation

Neutrophils are recognised to play a pivotal role at the interface between innate and acquired immunities following their recruitment to inflamed tissues and lymphoid organs. While neutrophil trafficking through blood vessels has been extensively studied, the molecular mechanisms regulating their mi...

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Autores principales: Arokiasamy, Samantha, Zakian, Christian, Dilliway, Jessica, Wang, Wen, Nourshargh, Sussan, Voisin, Mathieu-Benoit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5347029/
https://www.ncbi.nlm.nih.gov/pubmed/28287124
http://dx.doi.org/10.1038/srep44189
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author Arokiasamy, Samantha
Zakian, Christian
Dilliway, Jessica
Wang, Wen
Nourshargh, Sussan
Voisin, Mathieu-Benoit
author_facet Arokiasamy, Samantha
Zakian, Christian
Dilliway, Jessica
Wang, Wen
Nourshargh, Sussan
Voisin, Mathieu-Benoit
author_sort Arokiasamy, Samantha
collection PubMed
description Neutrophils are recognised to play a pivotal role at the interface between innate and acquired immunities following their recruitment to inflamed tissues and lymphoid organs. While neutrophil trafficking through blood vessels has been extensively studied, the molecular mechanisms regulating their migration into the lymphatic system are still poorly understood. Here, we have analysed neutrophil-lymphatic vessel interactions in real time and in vivo using intravital confocal microscopy applied to inflamed cremaster muscles. We show that antigen sensitisation of the tissues induces a rapid but transient entry of tissue-infiltrated neutrophils into lymphatic vessels and subsequent crawling along the luminal side of the lymphatic endothelium. Interestingly, using mice deficient in both TNF receptors p55 and p75, chimeric animals and anti-TNFα antibody blockade we demonstrate that tissue-release of TNFα governs both neutrophil migration through the lymphatic endothelium and luminal crawling. Mechanistically, we show that TNFα primes directly the neutrophils to enter the lymphatic vessels in a strictly CCR7-dependent manner; and induces ICAM-1 up-regulation on lymphatic vessels, allowing neutrophils to crawl along the lumen of the lymphatic endothelium in an ICAM-1/MAC-1-dependent manner. Collectively, our findings demonstrate a new role for TNFα as a key regulator of neutrophil trafficking into and within lymphatic system in vivo.
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spelling pubmed-53470292017-03-14 Endogenous TNFα orchestrates the trafficking of neutrophils into and within lymphatic vessels during acute inflammation Arokiasamy, Samantha Zakian, Christian Dilliway, Jessica Wang, Wen Nourshargh, Sussan Voisin, Mathieu-Benoit Sci Rep Article Neutrophils are recognised to play a pivotal role at the interface between innate and acquired immunities following their recruitment to inflamed tissues and lymphoid organs. While neutrophil trafficking through blood vessels has been extensively studied, the molecular mechanisms regulating their migration into the lymphatic system are still poorly understood. Here, we have analysed neutrophil-lymphatic vessel interactions in real time and in vivo using intravital confocal microscopy applied to inflamed cremaster muscles. We show that antigen sensitisation of the tissues induces a rapid but transient entry of tissue-infiltrated neutrophils into lymphatic vessels and subsequent crawling along the luminal side of the lymphatic endothelium. Interestingly, using mice deficient in both TNF receptors p55 and p75, chimeric animals and anti-TNFα antibody blockade we demonstrate that tissue-release of TNFα governs both neutrophil migration through the lymphatic endothelium and luminal crawling. Mechanistically, we show that TNFα primes directly the neutrophils to enter the lymphatic vessels in a strictly CCR7-dependent manner; and induces ICAM-1 up-regulation on lymphatic vessels, allowing neutrophils to crawl along the lumen of the lymphatic endothelium in an ICAM-1/MAC-1-dependent manner. Collectively, our findings demonstrate a new role for TNFα as a key regulator of neutrophil trafficking into and within lymphatic system in vivo. Nature Publishing Group 2017-03-13 /pmc/articles/PMC5347029/ /pubmed/28287124 http://dx.doi.org/10.1038/srep44189 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Arokiasamy, Samantha
Zakian, Christian
Dilliway, Jessica
Wang, Wen
Nourshargh, Sussan
Voisin, Mathieu-Benoit
Endogenous TNFα orchestrates the trafficking of neutrophils into and within lymphatic vessels during acute inflammation
title Endogenous TNFα orchestrates the trafficking of neutrophils into and within lymphatic vessels during acute inflammation
title_full Endogenous TNFα orchestrates the trafficking of neutrophils into and within lymphatic vessels during acute inflammation
title_fullStr Endogenous TNFα orchestrates the trafficking of neutrophils into and within lymphatic vessels during acute inflammation
title_full_unstemmed Endogenous TNFα orchestrates the trafficking of neutrophils into and within lymphatic vessels during acute inflammation
title_short Endogenous TNFα orchestrates the trafficking of neutrophils into and within lymphatic vessels during acute inflammation
title_sort endogenous tnfα orchestrates the trafficking of neutrophils into and within lymphatic vessels during acute inflammation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5347029/
https://www.ncbi.nlm.nih.gov/pubmed/28287124
http://dx.doi.org/10.1038/srep44189
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