3-hydroxy-L-kynurenamine is an immunomodulatory biogenic amine
Autor(a) principal: | |
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Data de Publicação: | 2021 |
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/10451/49217 |
Resumo: | © The Author(s) 2021. 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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3-hydroxy-L-kynurenamine is an immunomodulatory biogenic amineAutoimmunityInflammationSkin diseases© The Author(s) 2021. 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/.Tryptophan catabolism is a major metabolic pathway utilized by several professional and non-professional antigen presenting cells to maintain immunological tolerance. Here we report that 3-hydroxy-L-kynurenamine (3-HKA) is a biogenic amine produced via an alternative pathway of tryptophan metabolism. In vitro, 3-HKA has an anti-inflammatory profile by inhibiting the IFN-γ mediated STAT1/NF-κΒ pathway in both mouse and human dendritic cells (DCs) with a consequent decrease in the release of pro-inflammatory chemokines and cytokines, most notably TNF, IL-6, and IL12p70. 3-HKA has protective effects in an experimental mouse model of psoriasis by decreasing skin thickness, erythema, scaling and fissuring, reducing TNF, IL-1β, IFN-γ, and IL-17 production, and inhibiting generation of effector CD8+ T cells. Similarly, in a mouse model of nephrotoxic nephritis, besides reducing inflammatory cytokines, 3-HKA improves proteinuria and serum urea nitrogen, overall ameliorating immune-mediated glomerulonephritis and renal dysfunction. Overall, we propose that this biogenic amine is a crucial component of tryptophan-mediated immune tolerance.The work was supported by the following grants: NIH-AG045223 and NIH-AI137198 to L.S.; the Swiss National Science Foundation, grant 310030_182528 to C.H.; Telethon GGP17094 and the Associazione Italiana per la Ricerca sul Cancro (AIRC; 19903) to F.F.; Sigrid Juselius Foundation to K.A.; NIH T32 DK007110 to S.C.; NIH-AI103338 and NIH-AI138552 to G.L.; NIH K12 GM102779/BETTR program to R.F.; Associazione Italiana per la Ricerca sul Cancro (AIRC 2019-23084) to U.G.; The Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (ZIG AR041181-11) to W.L.T. and M.G. European Union H2020 ERA project (No. 667824 – EXCELLtoINNOV) to M.V.Springer NatureRepositório da Universidade de LisboaClement, Cristina C.D’Alessandro, AngeloThangaswamy, SangeethaChalmers, SamanthaFurtado, RaquelSpada, SheilaMondanelli, GiadaIanni, FedericaGehrke, SarahGargaro, MarcoManni, GiorgiaCara, Luisa Carlota LopezRunge, PeterTsai, Wanxia LiKaraman, SinemArasa, JorgeFernandez-Rodriguez, RubenBeck, AmandaMacchiarulo, AntonioGadina, MassimoHalin, CorneliaFallarino, FrancescaSkobe, MihaelaVeldhoen, MarcMoretti, SimoneFormenti, SilviaDemaria, SandraSoni, Rajesh K.Galarini, RobertaSardella, RoccaldoLauvau, GregoirePutterman, ChaimAlitalo, KariGrohmann, UrsulaSantambrogio, Laura2021-07-29T14:36:03Z20212021-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/49217engNat Commun. 2021 Jul 21;12(1):444710.1038/s41467-021-24785-32041-1723info: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:RCAAP2023-11-08T16:52:43Zoai:repositorio.ul.pt:10451/49217Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:00:50.595664Repositório 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 |
3-hydroxy-L-kynurenamine is an immunomodulatory biogenic amine |
title |
3-hydroxy-L-kynurenamine is an immunomodulatory biogenic amine |
spellingShingle |
3-hydroxy-L-kynurenamine is an immunomodulatory biogenic amine Clement, Cristina C. Autoimmunity Inflammation Skin diseases |
title_short |
3-hydroxy-L-kynurenamine is an immunomodulatory biogenic amine |
title_full |
3-hydroxy-L-kynurenamine is an immunomodulatory biogenic amine |
title_fullStr |
3-hydroxy-L-kynurenamine is an immunomodulatory biogenic amine |
title_full_unstemmed |
3-hydroxy-L-kynurenamine is an immunomodulatory biogenic amine |
title_sort |
3-hydroxy-L-kynurenamine is an immunomodulatory biogenic amine |
author |
Clement, Cristina C. |
author_facet |
Clement, Cristina C. D’Alessandro, Angelo Thangaswamy, Sangeetha Chalmers, Samantha Furtado, Raquel Spada, Sheila Mondanelli, Giada Ianni, Federica Gehrke, Sarah Gargaro, Marco Manni, Giorgia Cara, Luisa Carlota Lopez Runge, Peter Tsai, Wanxia Li Karaman, Sinem Arasa, Jorge Fernandez-Rodriguez, Ruben Beck, Amanda Macchiarulo, Antonio Gadina, Massimo Halin, Cornelia Fallarino, Francesca Skobe, Mihaela Veldhoen, Marc Moretti, Simone Formenti, Silvia Demaria, Sandra Soni, Rajesh K. Galarini, Roberta Sardella, Roccaldo Lauvau, Gregoire Putterman, Chaim Alitalo, Kari Grohmann, Ursula Santambrogio, Laura |
author_role |
author |
author2 |
D’Alessandro, Angelo Thangaswamy, Sangeetha Chalmers, Samantha Furtado, Raquel Spada, Sheila Mondanelli, Giada Ianni, Federica Gehrke, Sarah Gargaro, Marco Manni, Giorgia Cara, Luisa Carlota Lopez Runge, Peter Tsai, Wanxia Li Karaman, Sinem Arasa, Jorge Fernandez-Rodriguez, Ruben Beck, Amanda Macchiarulo, Antonio Gadina, Massimo Halin, Cornelia Fallarino, Francesca Skobe, Mihaela Veldhoen, Marc Moretti, Simone Formenti, Silvia Demaria, Sandra Soni, Rajesh K. Galarini, Roberta Sardella, Roccaldo Lauvau, Gregoire Putterman, Chaim Alitalo, Kari Grohmann, Ursula Santambrogio, Laura |
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 author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
dc.contributor.author.fl_str_mv |
Clement, Cristina C. D’Alessandro, Angelo Thangaswamy, Sangeetha Chalmers, Samantha Furtado, Raquel Spada, Sheila Mondanelli, Giada Ianni, Federica Gehrke, Sarah Gargaro, Marco Manni, Giorgia Cara, Luisa Carlota Lopez Runge, Peter Tsai, Wanxia Li Karaman, Sinem Arasa, Jorge Fernandez-Rodriguez, Ruben Beck, Amanda Macchiarulo, Antonio Gadina, Massimo Halin, Cornelia Fallarino, Francesca Skobe, Mihaela Veldhoen, Marc Moretti, Simone Formenti, Silvia Demaria, Sandra Soni, Rajesh K. Galarini, Roberta Sardella, Roccaldo Lauvau, Gregoire Putterman, Chaim Alitalo, Kari Grohmann, Ursula Santambrogio, Laura |
dc.subject.por.fl_str_mv |
Autoimmunity Inflammation Skin diseases |
topic |
Autoimmunity Inflammation Skin diseases |
description |
© The Author(s) 2021. 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 |
2021 |
dc.date.none.fl_str_mv |
2021-07-29T14:36:03Z 2021 2021-01-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10451/49217 |
url |
http://hdl.handle.net/10451/49217 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Nat Commun. 2021 Jul 21;12(1):4447 10.1038/s41467-021-24785-3 2041-1723 |
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openAccess |
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Springer Nature |
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Springer Nature |
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