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mTOR-Dependent Stimulation of IL20RA Orchestrates Immune Cell Trafficking through Lymphatic Endothelium in Patients with Crohn’s Disease
Crohn’s disease (CD) is a chronic inflammatory condition that can affect different portions of the gastrointestinal tract. Lymphatic drainage was demonstrated to be dysfunctional in CD pathogenesis, ultimately causing the failure of the resolution of intestinal inflammation. To investigate the molec...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721646/ https://www.ncbi.nlm.nih.gov/pubmed/31426584 http://dx.doi.org/10.3390/cells8080924 |
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author | Ungaro, Federica Garlatti, Valentina Massimino, Luca Spinelli, Antonino Carvello, Michele Sacchi, Matteo Spanò, Salvatore Colasante, Gaia Valassina, Nicholas Vetrano, Stefania Malesci, Alberto Peyrin-Biroulet, Laurent Danese, Silvio D’Alessio, Silvia |
author_facet | Ungaro, Federica Garlatti, Valentina Massimino, Luca Spinelli, Antonino Carvello, Michele Sacchi, Matteo Spanò, Salvatore Colasante, Gaia Valassina, Nicholas Vetrano, Stefania Malesci, Alberto Peyrin-Biroulet, Laurent Danese, Silvio D’Alessio, Silvia |
author_sort | Ungaro, Federica |
collection | PubMed |
description | Crohn’s disease (CD) is a chronic inflammatory condition that can affect different portions of the gastrointestinal tract. Lymphatic drainage was demonstrated to be dysfunctional in CD pathogenesis, ultimately causing the failure of the resolution of intestinal inflammation. To investigate the molecular mechanisms underlying these dysfunctions, we isolated human intestinal lymphatic endothelial cells (HILECs) from surgical specimens of patients undergoing resection for complicated CD (CD HILEC) and from a disease-free margin of surgical specimens of patients undergoing resection for cancer (healthy HILEC). Both cell types underwent transcriptomic profiling, and their barrier functionality was tested using a transwell-based co-culture system between HILEC and lamina propria mononuclear cells (LPMCs). Results showed CD HILEC displayed a peculiar transcriptomic signature that highlighted mTOR signaling as an orchestrator of leukocyte trafficking through the lymphatic barrier of CD patients. Moreover, we demonstrated that LPMC transmigration through the lymphatic endothelium of patients with CD depends on the capability of mTOR to trigger interleukin 20 receptor subunit α (IL20RA)-mediated intracellular signaling. Conclusively, our study suggests that leukocyte trafficking through the intestinal lymphatic microvasculature can be controlled by modulating IL20RA, thus leading to the resolution of chronic inflammation in patients with CD. |
format | Online Article Text |
id | pubmed-6721646 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-67216462019-09-10 mTOR-Dependent Stimulation of IL20RA Orchestrates Immune Cell Trafficking through Lymphatic Endothelium in Patients with Crohn’s Disease Ungaro, Federica Garlatti, Valentina Massimino, Luca Spinelli, Antonino Carvello, Michele Sacchi, Matteo Spanò, Salvatore Colasante, Gaia Valassina, Nicholas Vetrano, Stefania Malesci, Alberto Peyrin-Biroulet, Laurent Danese, Silvio D’Alessio, Silvia Cells Article Crohn’s disease (CD) is a chronic inflammatory condition that can affect different portions of the gastrointestinal tract. Lymphatic drainage was demonstrated to be dysfunctional in CD pathogenesis, ultimately causing the failure of the resolution of intestinal inflammation. To investigate the molecular mechanisms underlying these dysfunctions, we isolated human intestinal lymphatic endothelial cells (HILECs) from surgical specimens of patients undergoing resection for complicated CD (CD HILEC) and from a disease-free margin of surgical specimens of patients undergoing resection for cancer (healthy HILEC). Both cell types underwent transcriptomic profiling, and their barrier functionality was tested using a transwell-based co-culture system between HILEC and lamina propria mononuclear cells (LPMCs). Results showed CD HILEC displayed a peculiar transcriptomic signature that highlighted mTOR signaling as an orchestrator of leukocyte trafficking through the lymphatic barrier of CD patients. Moreover, we demonstrated that LPMC transmigration through the lymphatic endothelium of patients with CD depends on the capability of mTOR to trigger interleukin 20 receptor subunit α (IL20RA)-mediated intracellular signaling. Conclusively, our study suggests that leukocyte trafficking through the intestinal lymphatic microvasculature can be controlled by modulating IL20RA, thus leading to the resolution of chronic inflammation in patients with CD. MDPI 2019-08-18 /pmc/articles/PMC6721646/ /pubmed/31426584 http://dx.doi.org/10.3390/cells8080924 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ungaro, Federica Garlatti, Valentina Massimino, Luca Spinelli, Antonino Carvello, Michele Sacchi, Matteo Spanò, Salvatore Colasante, Gaia Valassina, Nicholas Vetrano, Stefania Malesci, Alberto Peyrin-Biroulet, Laurent Danese, Silvio D’Alessio, Silvia mTOR-Dependent Stimulation of IL20RA Orchestrates Immune Cell Trafficking through Lymphatic Endothelium in Patients with Crohn’s Disease |
title | mTOR-Dependent Stimulation of IL20RA Orchestrates Immune Cell Trafficking through Lymphatic Endothelium in Patients with Crohn’s Disease |
title_full | mTOR-Dependent Stimulation of IL20RA Orchestrates Immune Cell Trafficking through Lymphatic Endothelium in Patients with Crohn’s Disease |
title_fullStr | mTOR-Dependent Stimulation of IL20RA Orchestrates Immune Cell Trafficking through Lymphatic Endothelium in Patients with Crohn’s Disease |
title_full_unstemmed | mTOR-Dependent Stimulation of IL20RA Orchestrates Immune Cell Trafficking through Lymphatic Endothelium in Patients with Crohn’s Disease |
title_short | mTOR-Dependent Stimulation of IL20RA Orchestrates Immune Cell Trafficking through Lymphatic Endothelium in Patients with Crohn’s Disease |
title_sort | mtor-dependent stimulation of il20ra orchestrates immune cell trafficking through lymphatic endothelium in patients with crohn’s disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721646/ https://www.ncbi.nlm.nih.gov/pubmed/31426584 http://dx.doi.org/10.3390/cells8080924 |
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