Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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
_version_ 1783448389609848832
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
work_keys_str_mv AT ungarofederica mtordependentstimulationofil20raorchestratesimmunecelltraffickingthroughlymphaticendotheliuminpatientswithcrohnsdisease
AT garlattivalentina mtordependentstimulationofil20raorchestratesimmunecelltraffickingthroughlymphaticendotheliuminpatientswithcrohnsdisease
AT massiminoluca mtordependentstimulationofil20raorchestratesimmunecelltraffickingthroughlymphaticendotheliuminpatientswithcrohnsdisease
AT spinelliantonino mtordependentstimulationofil20raorchestratesimmunecelltraffickingthroughlymphaticendotheliuminpatientswithcrohnsdisease
AT carvellomichele mtordependentstimulationofil20raorchestratesimmunecelltraffickingthroughlymphaticendotheliuminpatientswithcrohnsdisease
AT sacchimatteo mtordependentstimulationofil20raorchestratesimmunecelltraffickingthroughlymphaticendotheliuminpatientswithcrohnsdisease
AT spanosalvatore mtordependentstimulationofil20raorchestratesimmunecelltraffickingthroughlymphaticendotheliuminpatientswithcrohnsdisease
AT colasantegaia mtordependentstimulationofil20raorchestratesimmunecelltraffickingthroughlymphaticendotheliuminpatientswithcrohnsdisease
AT valassinanicholas mtordependentstimulationofil20raorchestratesimmunecelltraffickingthroughlymphaticendotheliuminpatientswithcrohnsdisease
AT vetranostefania mtordependentstimulationofil20raorchestratesimmunecelltraffickingthroughlymphaticendotheliuminpatientswithcrohnsdisease
AT malescialberto mtordependentstimulationofil20raorchestratesimmunecelltraffickingthroughlymphaticendotheliuminpatientswithcrohnsdisease
AT peyrinbirouletlaurent mtordependentstimulationofil20raorchestratesimmunecelltraffickingthroughlymphaticendotheliuminpatientswithcrohnsdisease
AT danesesilvio mtordependentstimulationofil20raorchestratesimmunecelltraffickingthroughlymphaticendotheliuminpatientswithcrohnsdisease
AT dalessiosilvia mtordependentstimulationofil20raorchestratesimmunecelltraffickingthroughlymphaticendotheliuminpatientswithcrohnsdisease