Logo do repositório
 
Publicação

Antigen-driven colonic inflammation is associated with development of dysplasia in primary sclerosing cholangitis

2023Artigo científico Acesso aberto
Ver registo simples
dc.contributor.authorShaw, Dustin G.
dc.contributor.authorAguirre-Gamboa, Raúl
dc.contributor.authorVieira, Marcos C.
dc.contributor.authorGona, Saideep
dc.contributor.authorDiNardi, Nicholas
dc.contributor.authorWang, Anni
dc.contributor.authorDumaine, Anne
dc.contributor.authorGelderloos-Arends, Jody
dc.contributor.authorEarley, Zachary M.
dc.contributor.authorMeckel, Katherine R.
dc.contributor.authorCiszewski, Cezary
dc.contributor.authorCastillo, Anabella
dc.contributor.authorMonroe, Kelly
dc.contributor.authorTorres, Joana
dc.contributor.authorShah, Shailja C.
dc.contributor.authorColombel, Jean-Frédéric
dc.contributor.authorItzkowitz, Steven
dc.contributor.authorNewberry, Rodney
dc.contributor.authorCohen, Russell D.
dc.contributor.authorRubin, David T.
dc.contributor.authorQuince, Christopher
dc.contributor.authorCobey, Sarah
dc.contributor.authorJonkers, Iris H.
dc.contributor.authorWeber, Christopher R.
dc.contributor.authorPekow, Joel
dc.contributor.authorWilson, Patrick C.
dc.contributor.authorBarreiro, Luis B.
dc.contributor.authorJabri, Bana
dc.date.accessioned2023-06-16T13:44:19Z
dc.date.available2023-06-16T13:44:19Z
dc.date.issued2023
dc.description© The Author(s). Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.pt_PT
dc.description.abstractPrimary sclerosing cholangitis (PSC) is an immune-mediated disease of the bile ducts that co-occurs with inflammatory bowel disease (IBD) in almost 90% of cases. Colorectal cancer is a major complication of patients with PSC and IBD, and these patients are at a much greater risk compared to patients with IBD without concomitant PSC. Combining flow cytometry, bulk and single-cell transcriptomics, and T and B cell receptor repertoire analysis of right colon tissue from 65 patients with PSC, 108 patients with IBD and 48 healthy individuals we identified a unique adaptive inflammatory transcriptional signature associated with greater risk and shorter time to dysplasia in patients with PSC. This inflammatory signature is characterized by antigen-driven interleukin-17A (IL-17A)+ forkhead box P3 (FOXP3)+ CD4 T cells that express a pathogenic IL-17 signature, as well as an expansion of IgG-secreting plasma cells. These results suggest that the mechanisms that drive the emergence of dysplasia in PSC and IBD are distinct and provide molecular insights that could guide prevention of colorectal cancer in individuals with PSC.pt_PT
dc.description.sponsorshipThis work was supported by the Leona M. and Harry B. Helmsley Charitable trust (SHARE), the Digestive Diseases Research Core Center C-IID P30 DK42086 at the University of Chicago, the PSC Partners Seeking a Cure Canada and the Sczholtz Family Foundation. K.R.M. is supported by grant no. NS124187. S.C.S. is supported by an American Gastroenterological Association Research Scholar Award, Veterans Affairs Career Development Award (no. ICX002027A01) and the San Diego Digestive Diseases Research Center (no. P30 DK120515). C.Q. is supported by the BBSRC Core Strategic Programme Grant (BB/CSP1720/1, BBS/E/T/000PR9818 and BBS/E/T/000PR9817). I.H.J. is supported by a Rosalind Franklin Fellowship from the University of Groningen and a Netherlands Organization for Scientific Research VIDI grant no. 016.171.047. D.G.S. is supported by grant no. F30DK121470.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationNat Med. 2023 Jun 15pt_PT
dc.identifier.doi10.1038/s41591-023-02372-xpt_PT
dc.identifier.eissn1546-170X
dc.identifier.issn1078-8956
dc.identifier.urihttp://hdl.handle.net/10451/58252
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherSpringer Naturept_PT
dc.relation.publisherversionhttps://www.nature.com/nm/pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.titleAntigen-driven colonic inflammation is associated with development of dysplasia in primary sclerosing cholangitispt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.titleNature Medicinept_PT
person.familyNameTorres
person.givenNameJoana
person.identifier.orcid0000-0003-2895-5821
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication38a18ac5-f4d2-4748-adf8-d41eefac84ab
relation.isAuthorOfPublication.latestForDiscovery38a18ac5-f4d2-4748-adf8-d41eefac84ab

Ficheiros

Principais
A mostrar 1 - 1 de 1
Miniatura
Nome:
Antigen_colonic.pdf
Tamanho:
7.94 MB
Formato:
Adobe Portable Document Format
Ver/Abrir
Licença
A mostrar 1 - 1 de 1
Miniatura indisponível
Nome:
license.txt
Tamanho:
1.2 KB
Formato:
Item-specific license agreed upon to submission
Descrição:
Ver/Abrir

Coleções

FM - Artigos em Revistas Internacionais