Ex-Vivo Skin Explant Culture Is a Model for TSLP-Mediated Skin Barrier Immunity

The skin is the outermost barrier protecting the body from pathogenic invasion and environmental insults. Its breakdown initiates the start of skin inflammation. The epidermal growth factor (EGFR) on keratinocytes protects this barrier, and its dysfunction leads to atopic dermatitis-like skin diseas...

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Autores principales:	Thomas Bauer, Daniela Gubi, Jörg Klufa, Philipp Novoszel, Martin Holcmann, Maria Sibilia
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	skin EGFR Langerhans cell atopic inflammation TSLP barrier immunity Science Q
Acceso en línea:	https://doaj.org/article/f53435f55ffb48c2af4e18f36b8ad734
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spelling	oai:doaj.org-article:f53435f55ffb48c2af4e18f36b8ad7342021-11-25T18:11:26ZEx-Vivo Skin Explant Culture Is a Model for TSLP-Mediated Skin Barrier Immunity10.3390/life111112372075-1729https://doaj.org/article/f53435f55ffb48c2af4e18f36b8ad7342021-11-01T00:00:00Zhttps://www.mdpi.com/2075-1729/11/11/1237https://doaj.org/toc/2075-1729The skin is the outermost barrier protecting the body from pathogenic invasion and environmental insults. Its breakdown initiates the start of skin inflammation. The epidermal growth factor (EGFR) on keratinocytes protects this barrier, and its dysfunction leads to atopic dermatitis-like skin disease. One of the initial cytokines expressed upon skin barrier breach and during atopic dermatitis is TSLP. Here, we describe the expression and secretion of TSLP during EGFR inhibition and present an ex-vivo model, which mimics the early events after barrier insult. Skin explants floated on culture medium at 32 °C released TSLP in parallel to the activation of the resident Langerhans cell network. We could further show the up-regulation and activation of the AP-1 family of transcription factors during atopic-like skin inflammation and its involvement in TSLP production from the skin explant cultures. Inhibition of the c-Jun N-terminal kinase pathway led to a dose-dependent blunting of TSLP release. These data indicate the involvement of AP-1 during the early stages of atopic-like skin inflammation and highlight a novel therapeutic approach by targeting it. Therefore, skin explant cultures mimic the early events during skin barrier immunity and provide a suitable model to test therapeutic intervention.Thomas BauerDaniela GubiJörg KlufaPhilipp NovoszelMartin HolcmannMaria SibiliaMDPI AGarticleskinEGFRLangerhans cellatopic inflammationTSLPbarrier immunityScienceQENLife, Vol 11, Iss 1237, p 1237 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	skin EGFR Langerhans cell atopic inflammation TSLP barrier immunity Science Q
spellingShingle	skin EGFR Langerhans cell atopic inflammation TSLP barrier immunity Science Q Thomas Bauer Daniela Gubi Jörg Klufa Philipp Novoszel Martin Holcmann Maria Sibilia Ex-Vivo Skin Explant Culture Is a Model for TSLP-Mediated Skin Barrier Immunity
description	The skin is the outermost barrier protecting the body from pathogenic invasion and environmental insults. Its breakdown initiates the start of skin inflammation. The epidermal growth factor (EGFR) on keratinocytes protects this barrier, and its dysfunction leads to atopic dermatitis-like skin disease. One of the initial cytokines expressed upon skin barrier breach and during atopic dermatitis is TSLP. Here, we describe the expression and secretion of TSLP during EGFR inhibition and present an ex-vivo model, which mimics the early events after barrier insult. Skin explants floated on culture medium at 32 °C released TSLP in parallel to the activation of the resident Langerhans cell network. We could further show the up-regulation and activation of the AP-1 family of transcription factors during atopic-like skin inflammation and its involvement in TSLP production from the skin explant cultures. Inhibition of the c-Jun N-terminal kinase pathway led to a dose-dependent blunting of TSLP release. These data indicate the involvement of AP-1 during the early stages of atopic-like skin inflammation and highlight a novel therapeutic approach by targeting it. Therefore, skin explant cultures mimic the early events during skin barrier immunity and provide a suitable model to test therapeutic intervention.
format	article
author	Thomas Bauer Daniela Gubi Jörg Klufa Philipp Novoszel Martin Holcmann Maria Sibilia
author_facet	Thomas Bauer Daniela Gubi Jörg Klufa Philipp Novoszel Martin Holcmann Maria Sibilia
author_sort	Thomas Bauer
title	Ex-Vivo Skin Explant Culture Is a Model for TSLP-Mediated Skin Barrier Immunity
title_short	Ex-Vivo Skin Explant Culture Is a Model for TSLP-Mediated Skin Barrier Immunity
title_full	Ex-Vivo Skin Explant Culture Is a Model for TSLP-Mediated Skin Barrier Immunity
title_fullStr	Ex-Vivo Skin Explant Culture Is a Model for TSLP-Mediated Skin Barrier Immunity
title_full_unstemmed	Ex-Vivo Skin Explant Culture Is a Model for TSLP-Mediated Skin Barrier Immunity
title_sort	ex-vivo skin explant culture is a model for tslp-mediated skin barrier immunity
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/f53435f55ffb48c2af4e18f36b8ad734
work_keys_str_mv	AT thomasbauer exvivoskinexplantcultureisamodelfortslpmediatedskinbarrierimmunity AT danielagubi exvivoskinexplantcultureisamodelfortslpmediatedskinbarrierimmunity AT jorgklufa exvivoskinexplantcultureisamodelfortslpmediatedskinbarrierimmunity AT philippnovoszel exvivoskinexplantcultureisamodelfortslpmediatedskinbarrierimmunity AT martinholcmann exvivoskinexplantcultureisamodelfortslpmediatedskinbarrierimmunity AT mariasibilia exvivoskinexplantcultureisamodelfortslpmediatedskinbarrierimmunity
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Ex-Vivo Skin Explant Culture Is a Model for TSLP-Mediated Skin Barrier Immunity

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