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

Detalhes bibliográficos
Autor(a) principal: Shaw, Dustin G.
Data de Publicação: 2023
Outros Autores: 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
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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spelling 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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dc.relation.none.fl_str_mv Nat Med. 2023 Jun 15
1078-8956
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1546-170X
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