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Development and characterization of a human Th17‐driven ex vivo skin inflammation model

Skin models mimicking features of psoriasis‐related inflammation are needed to support the development of new drugs in dermatology. Reconstructed skin models lack tissue complexity, including a fully competent skin barrier, and presence and/or diversity of immune cells. Here, we describe InflammaSki...

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Autores principales: Jardet, Claire, David, Anthony, Braun, Emilie, Descargues, Pascal, Grolleau, Jean‐Louis, Hebsgaard, Josephine, Norsgaard, Hanne, Lovato, Paola
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693225/
https://www.ncbi.nlm.nih.gov/pubmed/32737987
http://dx.doi.org/10.1111/exd.14160
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author Jardet, Claire
David, Anthony
Braun, Emilie
Descargues, Pascal
Grolleau, Jean‐Louis
Hebsgaard, Josephine
Norsgaard, Hanne
Lovato, Paola
author_facet Jardet, Claire
David, Anthony
Braun, Emilie
Descargues, Pascal
Grolleau, Jean‐Louis
Hebsgaard, Josephine
Norsgaard, Hanne
Lovato, Paola
author_sort Jardet, Claire
collection PubMed
description Skin models mimicking features of psoriasis‐related inflammation are needed to support the development of new drugs in dermatology. Reconstructed skin models lack tissue complexity, including a fully competent skin barrier, and presence and/or diversity of immune cells. Here, we describe InflammaSkin®, a novel human Th17‐driven ex vivo skin inflammation model. In this model, skin‐resident T cells are in situ activated by intradermal injection of anti‐CD3 and anti‐CD28 antibodies and Th17 cell polarization is sustained by culture in a chemically defined medium supplemented with IL‐1β, IL‐23 and TGF‐β for seven days. The acquired Th17 signature is demonstrated by the sustained secretion of IL‐17A, IL‐17AF, IL‐17F, IL‐22, IFN‐γ, and to some degree IL‐15 and TNF‐α observed in the activated ex vivo skin inflammation model compared with the non‐activated skin model control. Furthermore, expression of S100A7 and Keratin‐16 by keratinocytes and loss of epidermal structure integrity occur subsequently to in situ Th17cell activation, demonstrating cellular crosstalk between Th17 cells and keratinocytes. Finally, we demonstrate the use of this model to investigate the modulation of the IL‐23/IL‐17 immune axis by topically applied anti‐inflammatory compounds. Taken together, we show that by in situ activation of skin‐resident Th17 cells, the InflammaSkin® model reproduces aspects of inflammatory responses observed in psoriatic lesions and could be used as a translational tool to assess efficacy of test compounds.
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spelling pubmed-76932252020-12-11 Development and characterization of a human Th17‐driven ex vivo skin inflammation model Jardet, Claire David, Anthony Braun, Emilie Descargues, Pascal Grolleau, Jean‐Louis Hebsgaard, Josephine Norsgaard, Hanne Lovato, Paola Exp Dermatol Original Research Article Skin models mimicking features of psoriasis‐related inflammation are needed to support the development of new drugs in dermatology. Reconstructed skin models lack tissue complexity, including a fully competent skin barrier, and presence and/or diversity of immune cells. Here, we describe InflammaSkin®, a novel human Th17‐driven ex vivo skin inflammation model. In this model, skin‐resident T cells are in situ activated by intradermal injection of anti‐CD3 and anti‐CD28 antibodies and Th17 cell polarization is sustained by culture in a chemically defined medium supplemented with IL‐1β, IL‐23 and TGF‐β for seven days. The acquired Th17 signature is demonstrated by the sustained secretion of IL‐17A, IL‐17AF, IL‐17F, IL‐22, IFN‐γ, and to some degree IL‐15 and TNF‐α observed in the activated ex vivo skin inflammation model compared with the non‐activated skin model control. Furthermore, expression of S100A7 and Keratin‐16 by keratinocytes and loss of epidermal structure integrity occur subsequently to in situ Th17cell activation, demonstrating cellular crosstalk between Th17 cells and keratinocytes. Finally, we demonstrate the use of this model to investigate the modulation of the IL‐23/IL‐17 immune axis by topically applied anti‐inflammatory compounds. Taken together, we show that by in situ activation of skin‐resident Th17 cells, the InflammaSkin® model reproduces aspects of inflammatory responses observed in psoriatic lesions and could be used as a translational tool to assess efficacy of test compounds. John Wiley and Sons Inc. 2020-08-25 2020-10 /pmc/articles/PMC7693225/ /pubmed/32737987 http://dx.doi.org/10.1111/exd.14160 Text en © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Research Article
Jardet, Claire
David, Anthony
Braun, Emilie
Descargues, Pascal
Grolleau, Jean‐Louis
Hebsgaard, Josephine
Norsgaard, Hanne
Lovato, Paola
Development and characterization of a human Th17‐driven ex vivo skin inflammation model
title Development and characterization of a human Th17‐driven ex vivo skin inflammation model
title_full Development and characterization of a human Th17‐driven ex vivo skin inflammation model
title_fullStr Development and characterization of a human Th17‐driven ex vivo skin inflammation model
title_full_unstemmed Development and characterization of a human Th17‐driven ex vivo skin inflammation model
title_short Development and characterization of a human Th17‐driven ex vivo skin inflammation model
title_sort development and characterization of a human th17‐driven ex vivo skin inflammation model
topic Original Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693225/
https://www.ncbi.nlm.nih.gov/pubmed/32737987
http://dx.doi.org/10.1111/exd.14160
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