Tnfa signaling through Tnfr2 protects skin against oxidative stress–induced inflammation
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2014 |
| 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/10451/44949 |
Resumo: | © 2014 Candel et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
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Tnfa signaling through Tnfr2 protects skin against oxidative stress–induced inflammation© 2014 Candel et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.TNFα overexpression has been associated with several chronic inflammatory diseases, including psoriasis, lichen planus, rheumatoid arthritis, and inflammatory bowel disease. Paradoxically, numerous studies have reported new-onset psoriasis and lichen planus following TNFα antagonist therapy. Here, we show that genetic inhibition of Tnfa and Tnfr2 in zebrafish results in the mobilization of neutrophils to the skin. Using combinations of fluorescent reporter transgenes, fluorescence microscopy, and flow cytometry, we identified the local production of dual oxidase 1 (Duox1)-derived H₂O₂ by Tnfa- and Tnfr2-deficient keratinocytes as a trigger for the activation of the master inflammation transcription factor NF-κB, which then promotes the induction of genes encoding pro-inflammatory molecules. In addition, pharmacological inhibition of Duox1 completely abrogated skin inflammation, placing Duox1-derived H₂O₂ upstream of this positive feedback inflammatory loop. Strikingly, DUOX1 was drastically induced in the skin lesions of psoriasis and lichen planus patients. These results reveal a crucial role for TNFα/TNFR2 axis in the protection of the skin against DUOX1-mediated oxidative stress and could establish new therapeutic targets for skin inflammatory disorders.This work was supported by the Spanish Ministry of Science and Innovation (grants BIO2011-23400 and CSD2007-00002 to VM, and PhD fellowship toSC, all co-funded with Fondos Europeos de Desarrollo Regional/European Regional Development Funds), the Fundación Séneca-Murcia (grant 04538/GERM/06 toVM and PhD fellowship to RE-P), Fundação para a Ciência e Tecnologia (PhD fellowship to SdO, SFRH/BD/62674/2009), a Medical Research Council Senior Clinicalfellowship to SAR (G0701932), and the European 7th Framework Initial Training Network FishForPharma (PhD fellowship to SDT, PITG-GA-2011-289209). Thefunders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.PLOSRepositório da Universidade de LisboaCandel, SergioDe Oliveira, SofiaLópez-Muñoz, AzucenaGarcía-Moreno, DianaEspín-Palazón, RaquelTyrkalska, Sylwia D.Cayuela, María L.Renshaw, Stephen A.Corbalán-Vélez, RaúlVidal-Abarca, InmaculadaTsai, Huai-JenMeseguer, JoséSepulcre, María P.Mulero, Victoriano2020-11-20T15:02:08Z20142014-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/44949engPLoS Biol. 2014 May 6;12(5):e10018551544-917310.1371/journal.pbio.10018551545-7885info: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:RCAAP2023-11-08T16:46:19Zoai:repositorio.ul.pt:10451/44949Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:57:26.289054Repositório 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 |
Tnfa signaling through Tnfr2 protects skin against oxidative stress–induced inflammation |
| title |
Tnfa signaling through Tnfr2 protects skin against oxidative stress–induced inflammation |
| spellingShingle |
Tnfa signaling through Tnfr2 protects skin against oxidative stress–induced inflammation Candel, Sergio |
| title_short |
Tnfa signaling through Tnfr2 protects skin against oxidative stress–induced inflammation |
| title_full |
Tnfa signaling through Tnfr2 protects skin against oxidative stress–induced inflammation |
| title_fullStr |
Tnfa signaling through Tnfr2 protects skin against oxidative stress–induced inflammation |
| title_full_unstemmed |
Tnfa signaling through Tnfr2 protects skin against oxidative stress–induced inflammation |
| title_sort |
Tnfa signaling through Tnfr2 protects skin against oxidative stress–induced inflammation |
| author |
Candel, Sergio |
| author_facet |
Candel, Sergio De Oliveira, Sofia López-Muñoz, Azucena García-Moreno, Diana Espín-Palazón, Raquel Tyrkalska, Sylwia D. Cayuela, María L. Renshaw, Stephen A. Corbalán-Vélez, Raúl Vidal-Abarca, Inmaculada Tsai, Huai-Jen Meseguer, José Sepulcre, María P. Mulero, Victoriano |
| author_role |
author |
| author2 |
De Oliveira, Sofia López-Muñoz, Azucena García-Moreno, Diana Espín-Palazón, Raquel Tyrkalska, Sylwia D. Cayuela, María L. Renshaw, Stephen A. Corbalán-Vélez, Raúl Vidal-Abarca, Inmaculada Tsai, Huai-Jen Meseguer, José Sepulcre, María P. Mulero, Victoriano |
| author2_role |
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 |
Candel, Sergio De Oliveira, Sofia López-Muñoz, Azucena García-Moreno, Diana Espín-Palazón, Raquel Tyrkalska, Sylwia D. Cayuela, María L. Renshaw, Stephen A. Corbalán-Vélez, Raúl Vidal-Abarca, Inmaculada Tsai, Huai-Jen Meseguer, José Sepulcre, María P. Mulero, Victoriano |
| description |
© 2014 Candel et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| publishDate |
2014 |
| dc.date.none.fl_str_mv |
2014 2014-01-01T00:00:00Z 2020-11-20T15:02:08Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10451/44949 |
| url |
http://hdl.handle.net/10451/44949 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
PLoS Biol. 2014 May 6;12(5):e1001855 1544-9173 10.1371/journal.pbio.1001855 1545-7885 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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PLOS |
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PLOS |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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