{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:35:57Z","timestamp":1790393757754,"version":"4.1.0"},"reference-count":33,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2019,8,18]],"date-time":"2019-08-18T00:00:00Z","timestamp":1566086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["RBFR12VP3Q_002 and GR-2011-02348069"],"award-info":[{"award-number":["RBFR12VP3Q_002 and GR-2011-02348069"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010767","name":"Innovative Medicines Initiative","doi-asserted-by":"publisher","award":["Joint Undertaking BTCure (115142)"],"award-info":[{"award-number":["Joint Undertaking BTCure (115142)"]}],"id":[{"id":"10.13039\/501100010767","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Crohn\u2019s 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 \u03b1 (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.<\/jats:p>","DOI":"10.3390\/cells8080924","type":"journal-article","created":{"date-parts":[[2019,8,19]],"date-time":"2019-08-19T06:10:14Z","timestamp":1566195014000},"page":"924","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["mTOR-Dependent Stimulation of IL20RA Orchestrates Immune Cell Trafficking through Lymphatic Endothelium in Patients with Crohn\u2019s Disease"],"prefix":"10.3390","volume":"8","author":[{"given":"Federica","family":"Ungaro","sequence":"first","affiliation":[{"name":"IBD Center, Laboratory of Gastrointestinal Immunopathology, Humanitas Clinical and Research Center, Rozzano, 20089 Milan, Italy"},{"name":"Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20090 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Garlatti","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20090 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3975-9148","authenticated-orcid":false,"given":"Luca","family":"Massimino","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonino","family":"Spinelli","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20090 Milan, Italy"},{"name":"Colon and Rectal Surgery Unit, Humanitas Clinical and Research Center, Rozzano, 20089 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8650-2321","authenticated-orcid":false,"given":"Michele","family":"Carvello","sequence":"additional","affiliation":[{"name":"Colon and Rectal Surgery Unit, Humanitas Clinical and Research Center, Rozzano, 20089 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Sacchi","sequence":"additional","affiliation":[{"name":"Colon and Rectal Surgery Unit, Humanitas Clinical and Research Center, Rozzano, 20089 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Span\u00f2","sequence":"additional","affiliation":[{"name":"IBD Center, Laboratory of Gastrointestinal Immunopathology, Humanitas Clinical and Research Center, Rozzano, 20089 Milan, Italy"},{"name":"Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20090 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaia","family":"Colasante","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Valassina","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Vetrano","sequence":"additional","affiliation":[{"name":"IBD Center, Laboratory of Gastrointestinal Immunopathology, Humanitas Clinical and Research Center, Rozzano, 20089 Milan, Italy"},{"name":"Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20090 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Malesci","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnologies and Translational Medicine, University of Milan, 200129 Milan, Italy"},{"name":"Department of Gastroenterology, Humanitas Clinical and Research Center, Rozzano, 20089 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Peyrin-Biroulet","sequence":"additional","affiliation":[{"name":"Inserm Ngere and Nancy University Hospital, Lorraine University, 54500 Vandoeuvre-l\u00e8s-Nancy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvio","family":"Danese","sequence":"additional","affiliation":[{"name":"IBD Center, Laboratory of Gastrointestinal Immunopathology, Humanitas Clinical and Research Center, Rozzano, 20089 Milan, Italy"},{"name":"Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20090 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"D\u2019Alessio","sequence":"additional","affiliation":[{"name":"IBD Center, Laboratory of Gastrointestinal Immunopathology, Humanitas Clinical and Research Center, Rozzano, 20089 Milan, Italy"},{"name":"Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20090 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,8,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1016\/S0140-6736(16)31711-1","article-title":"Crohn\u2019s disease","volume":"389","author":"Torres","year":"2017","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3863","DOI":"10.1172\/JCI72189","article-title":"VEGF-C-dependent stimulation of lymphatic function ameliorates experimental inflammatory bowel disease","volume":"124","author":"Correale","year":"2014","journal-title":"J. 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