Cutaneous Immune Cell-Microbiota Interactions Are Controlled by Epidermal JunB/AP-1

Atopic dermatitis (AD) is a multi-factorial skin disease with a complex inflammatory signature including type 2 and type 17 activation. Although colonization by S. aureus is common in AD, the mechanisms rendering an organism prone to dysbiosis, and the role of IL-17A in the control of S. aureus-indu...

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Detalles Bibliográficos
Autores: Uluçkan, Azge, Jimenez Maria, M, Roediger, Ben, Schnabl, Jakob, Díez-Córdova, Lucía T, Troulé, Kevin, Weninger, Wolfgang, Wagner, Erwin Friedrich
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/9331
Acceso en línea:http://hdl.handle.net/20.500.12105/9331
Access Level:acceso abierto
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spelling Cutaneous Immune Cell-Microbiota Interactions Are Controlled by Epidermal JunB/AP-1Uluçkan, AzgeJimenez Maria, MRoediger, BenSchnabl, JakobDíez-Córdova, Lucía TTroulé, KevinWeninger, WolfgangWagner, Erwin FriedrichAtopic dermatitis (AD) is a multi-factorial skin disease with a complex inflammatory signature including type 2 and type 17 activation. Although colonization by S. aureus is common in AD, the mechanisms rendering an organism prone to dysbiosis, and the role of IL-17A in the control of S. aureus-induced skin inflammation, are not well understood. Here, we show several pathological aspects of AD, including type 2/type 17 immune responses, elevated IgE, barrier dysfunction, pruritus, and importantly, spontaneous S. aureus colonization in JunBΔep mice, with a large transcriptomic overlap with AD. Additionally, using Rag1-/- mice, we demonstrate that adaptive immune cells are necessary for protection against S. aureus colonization. Prophylactic antibiotics, but not antibiotics after established dysbiosis, reduce IL-17A expression and skin inflammation, examined using Il17a-eGFP reporter mice. Mechanistically, keratinocytes lacking JunB exhibit higher MyD88 levels in vitro and in vivo, previously shown to regulate S. aureus colonization. In conclusion, our data identify JunB as an upstream regulator of microbiota-immune cell interactions and characterize the IL-17A response upon spontaneous dysbiosis.Cell PressMinisterio de Economía y Competitividad (España)Unión Europea. Comisión Europea. European Research Council (ERC)20202020-03-2520192019-10-2220192019-10-22journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfapplication/pdfhttp://hdl.handle.net/20.500.12105/9331reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución-NoComercial-CompartirIgual 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/93312026-06-12T12:43:37Z
dc.title.none.fl_str_mv Cutaneous Immune Cell-Microbiota Interactions Are Controlled by Epidermal JunB/AP-1
title Cutaneous Immune Cell-Microbiota Interactions Are Controlled by Epidermal JunB/AP-1
spellingShingle Cutaneous Immune Cell-Microbiota Interactions Are Controlled by Epidermal JunB/AP-1
Uluçkan, Azge
title_short Cutaneous Immune Cell-Microbiota Interactions Are Controlled by Epidermal JunB/AP-1
title_full Cutaneous Immune Cell-Microbiota Interactions Are Controlled by Epidermal JunB/AP-1
title_fullStr Cutaneous Immune Cell-Microbiota Interactions Are Controlled by Epidermal JunB/AP-1
title_full_unstemmed Cutaneous Immune Cell-Microbiota Interactions Are Controlled by Epidermal JunB/AP-1
title_sort Cutaneous Immune Cell-Microbiota Interactions Are Controlled by Epidermal JunB/AP-1
dc.creator.none.fl_str_mv Uluçkan, Azge
Jimenez Maria, M
Roediger, Ben
Schnabl, Jakob
Díez-Córdova, Lucía T
Troulé, Kevin
Weninger, Wolfgang
Wagner, Erwin Friedrich
author Uluçkan, Azge
author_facet Uluçkan, Azge
Jimenez Maria, M
Roediger, Ben
Schnabl, Jakob
Díez-Córdova, Lucía T
Troulé, Kevin
Weninger, Wolfgang
Wagner, Erwin Friedrich
author_role author
author2 Jimenez Maria, M
Roediger, Ben
Schnabl, Jakob
Díez-Córdova, Lucía T
Troulé, Kevin
Weninger, Wolfgang
Wagner, Erwin Friedrich
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
Unión Europea. Comisión Europea. European Research Council (ERC)
description Atopic dermatitis (AD) is a multi-factorial skin disease with a complex inflammatory signature including type 2 and type 17 activation. Although colonization by S. aureus is common in AD, the mechanisms rendering an organism prone to dysbiosis, and the role of IL-17A in the control of S. aureus-induced skin inflammation, are not well understood. Here, we show several pathological aspects of AD, including type 2/type 17 immune responses, elevated IgE, barrier dysfunction, pruritus, and importantly, spontaneous S. aureus colonization in JunBΔep mice, with a large transcriptomic overlap with AD. Additionally, using Rag1-/- mice, we demonstrate that adaptive immune cells are necessary for protection against S. aureus colonization. Prophylactic antibiotics, but not antibiotics after established dysbiosis, reduce IL-17A expression and skin inflammation, examined using Il17a-eGFP reporter mice. Mechanistically, keratinocytes lacking JunB exhibit higher MyD88 levels in vitro and in vivo, previously shown to regulate S. aureus colonization. In conclusion, our data identify JunB as an upstream regulator of microbiota-immune cell interactions and characterize the IL-17A response upon spontaneous dysbiosis.
publishDate 2019
dc.date.none.fl_str_mv 2019
2019-10-22
2019
2019-10-22
2020
2020-03-25
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/9331
url http://hdl.handle.net/20.500.12105/9331
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución-NoComercial-CompartirIgual 4.0 Internacional
http://creativecommons.org/licenses/by-nc-sa/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución-NoComercial-CompartirIgual 4.0 Internacional
http://creativecommons.org/licenses/by-nc-sa/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Cell Press
publisher.none.fl_str_mv Cell Press
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812455

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