{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T02:33:39Z","timestamp":1789785219342,"version":"4.0.1"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"vor","delay-in-days":9,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008373","name":"Takeda Pharmaceutical Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008373","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>We recently identified a population of pro-inflammatory intestinal CCR5+Th17-cells (proinflammatory Th17, pTh17) associated with intestinal inflammation in Crohn\u2019s Disease (CD) and activated by CD-associated adherent-invasive Escherichia coli. Here, we report that intestinal pTh17-cells in CD expressed genes characteristic of tissue-resident memory T-cells (TRM). They expressed high levels of CD69 and CD103 on the cell surface and accumulated in the intraepithelial lymphocyte (IEL) compartment in CD. Consistently, single T-cell RNA sequencing in CD unveiled that intraepithelial Th17-cells displayed a gene signature of activated pTh17-cells.In peripheral blood, pTh17-cells with gut-homing potential were hardly detectable. Conversely, conventional CCR5-Th17-cells (\u201ccTh17\u201d) were present and expressed increased levels of \u03b14\u03b27-integrin in the blood of IBD patients. Consistently, intestinal cTh17-cells were reduced after treatment with vedolizumab, which blocks \u03b14\u03b27-integrin-mediated gut-homing of lymphocytes. Importantly, unresponsiveness to vedolizumab in CD was associated with increased frequencies of preexisting intestinal pTh17-cells with high sensitivity and specificity. We conclude that intestinal pTh17-cells are tissue-resident cells, which could be generated from circulating cTh17 precursor cells in the gut. Moreover, our findings are consistent with a key pathogenic role of intraepithelial Th17-cells in CD and suggest that monitoring intestinal pTh17-cells may predict unresponsiveness to vedolizumab.<\/jats:p>","DOI":"10.1093\/ecco-jcc\/jjag055","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T11:49:08Z","timestamp":1776858548000},"source":"Crossref","is-referenced-by-count":2,"title":["Pro-inflammatory intestinal Th17-cells are tissue-resident, accumulate in the epithelia in Crohn\u2019s disease, and predict unresponsiveness to vedolizumab"],"prefix":"10.1093","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8199-3128","authenticated-orcid":false,"given":"Moira","family":"Paroni","sequence":"first","affiliation":[{"name":"Department of Biosciences, Dipartimento di Eccellenza 2023-2027, Universita\u0300 degli Studi di Milano , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Faggiano","sequence":"additional","affiliation":[{"name":"National Institute of Molecular Genetics (INGM) \u201cRomeo ed Enrica Invernizzi\u201d , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Righetti","sequence":"additional","affiliation":[{"name":"National Institute of Molecular Genetics (INGM) \u201cRomeo ed Enrica Invernizzi\u201d , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Dusetti","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Dipartimento di Eccellenza 2023-2027, Universita\u0300 degli Studi di Milano , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0602-5335","authenticated-orcid":false,"given":"Valeria","family":"Ranzani","sequence":"additional","affiliation":[{"name":"National Institute of Molecular Genetics (INGM) \u201cRomeo ed Enrica Invernizzi\u201d , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7763-4421","authenticated-orcid":false,"given":"Giorgia","family":"Moschetti","sequence":"additional","affiliation":[{"name":"National Institute of Molecular Genetics (INGM) \u201cRomeo ed Enrica Invernizzi\u201d , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Noviello","sequence":"additional","affiliation":[{"name":"Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico , Milan,","place":["Italy"]},{"name":"Department of Pathophysiology and Transplantation, Universita\u0300 degli Studi di Milano , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Vasco","sequence":"additional","affiliation":[{"name":"National Institute of Molecular Genetics (INGM) \u201cRomeo ed Enrica Invernizzi\u201d , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1558-8604","authenticated-orcid":false,"given":"Maurizio","family":"Vecchi","sequence":"additional","affiliation":[{"name":"Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico , Milan,","place":["Italy"]},{"name":"Department of Pathophysiology and Transplantation, Universita\u0300 degli Studi di Milano , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Landini","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Dipartimento di Eccellenza 2023-2027, Universita\u0300 degli Studi di Milano , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Facciotti","sequence":"additional","affiliation":[{"name":"Department Biotechnology and Biosciences, Universit\u00e0 Milano-Bicocca , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Abrignani","sequence":"additional","affiliation":[{"name":"National Institute of Molecular Genetics (INGM) \u201cRomeo ed Enrica Invernizzi\u201d , Milan,","place":["Italy"]},{"name":"DISCCO, Department of Clinical Science and Community Health, Dipartimento di Eccellenza 2023-27, Universit\u00e0 degli studi di Milano , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8077-8175","authenticated-orcid":false,"given":"Flavio","family":"Caprioli","sequence":"additional","affiliation":[{"name":"Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico , Milan,","place":["Italy"]},{"name":"Department of Pathophysiology and Transplantation, Universita\u0300 degli Studi di Milano , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Geginat","sequence":"additional","affiliation":[{"name":"National Institute of Molecular Genetics (INGM) \u201cRomeo ed Enrica Invernizzi\u201d , Milan,","place":["Italy"]},{"name":"DISCCO, Department of Clinical Science and Community Health, Dipartimento di Eccellenza 2023-27, Universit\u00e0 degli studi di Milano , 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