Antigen-driven colonic inflammation is associated with development of dysplasia in primary sclerosing cholangitis
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Outros Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10451/58252 |
Resumo: | © 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/. |
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Antigen-driven colonic inflammation is associated with development of dysplasia in primary sclerosing cholangitis© 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/.Primary 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.This 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.Springer NatureRepositório da Universidade de LisboaShaw, Dustin G.Aguirre-Gamboa, RaúlVieira, Marcos C.Gona, SaideepDiNardi, NicholasWang, AnniDumaine, AnneGelderloos-Arends, JodyEarley, Zachary M.Meckel, Katherine R.Ciszewski, CezaryCastillo, AnabellaMonroe, KellyTorres, JoanaShah, Shailja C.Colombel, Jean-FrédéricItzkowitz, StevenNewberry, RodneyCohen, Russell D.Rubin, David T.Quince, ChristopherCobey, SarahJonkers, Iris H.Weber, Christopher R.Pekow, JoelWilson, Patrick C.Barreiro, Luis B.Jabri, Bana2023-06-16T13:44:19Z20232023-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/58252engNat Med. 2023 Jun 151078-895610.1038/s41591-023-02372-x1546-170Xinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T17:07:01Zoai:repositorio.ul.pt:10451/58252Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:08:33.302144Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Antigen-driven colonic inflammation is associated with development of dysplasia in primary sclerosing cholangitis |
title |
Antigen-driven colonic inflammation is associated with development of dysplasia in primary sclerosing cholangitis |
spellingShingle |
Antigen-driven colonic inflammation is associated with development of dysplasia in primary sclerosing cholangitis Shaw, Dustin G. |
title_short |
Antigen-driven colonic inflammation is associated with development of dysplasia in primary sclerosing cholangitis |
title_full |
Antigen-driven colonic inflammation is associated with development of dysplasia in primary sclerosing cholangitis |
title_fullStr |
Antigen-driven colonic inflammation is associated with development of dysplasia in primary sclerosing cholangitis |
title_full_unstemmed |
Antigen-driven colonic inflammation is associated with development of dysplasia in primary sclerosing cholangitis |
title_sort |
Antigen-driven colonic inflammation is associated with development of dysplasia in primary sclerosing cholangitis |
author |
Shaw, Dustin G. |
author_facet |
Shaw, Dustin G. Aguirre-Gamboa, Raúl Vieira, Marcos C. Gona, Saideep DiNardi, Nicholas Wang, Anni Dumaine, Anne Gelderloos-Arends, Jody Earley, Zachary M. Meckel, Katherine R. Ciszewski, Cezary Castillo, Anabella Monroe, Kelly Torres, Joana Shah, Shailja C. Colombel, Jean-Frédéric Itzkowitz, Steven Newberry, Rodney Cohen, Russell D. Rubin, David T. Quince, Christopher Cobey, Sarah Jonkers, Iris H. Weber, Christopher R. Pekow, Joel Wilson, Patrick C. Barreiro, Luis B. Jabri, Bana |
author_role |
author |
author2 |
Aguirre-Gamboa, Raúl Vieira, Marcos C. Gona, Saideep DiNardi, Nicholas Wang, Anni Dumaine, Anne Gelderloos-Arends, Jody Earley, Zachary M. Meckel, Katherine R. Ciszewski, Cezary Castillo, Anabella Monroe, Kelly Torres, Joana Shah, Shailja C. Colombel, Jean-Frédéric Itzkowitz, Steven Newberry, Rodney Cohen, Russell D. Rubin, David T. Quince, Christopher Cobey, Sarah Jonkers, Iris H. Weber, Christopher R. Pekow, Joel Wilson, Patrick C. Barreiro, Luis B. Jabri, Bana |
author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
dc.contributor.author.fl_str_mv |
Shaw, Dustin G. Aguirre-Gamboa, Raúl Vieira, Marcos C. Gona, Saideep DiNardi, Nicholas Wang, Anni Dumaine, Anne Gelderloos-Arends, Jody Earley, Zachary M. Meckel, Katherine R. Ciszewski, Cezary Castillo, Anabella Monroe, Kelly Torres, Joana Shah, Shailja C. Colombel, Jean-Frédéric Itzkowitz, Steven Newberry, Rodney Cohen, Russell D. Rubin, David T. Quince, Christopher Cobey, Sarah Jonkers, Iris H. Weber, Christopher R. Pekow, Joel Wilson, Patrick C. Barreiro, Luis B. Jabri, Bana |
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/. |
publishDate |
2023 |
dc.date.none.fl_str_mv |
2023-06-16T13:44:19Z 2023 2023-01-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
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article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10451/58252 |
url |
http://hdl.handle.net/10451/58252 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
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Nat Med. 2023 Jun 15 1078-8956 10.1038/s41591-023-02372-x 1546-170X |
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Springer Nature |
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Springer Nature |
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