TSLP is a direct trigger for T cell migration in filaggrin-deficient skin equivalents

Abstract Mutations in the gene encoding for filaggrin (FLG) are major predisposing factors for atopic dermatitis (AD). Besides genetic predisposition, immunological dysregulations considerably contribute to its pathophysiology. For example, thymic stromal lymphopoietin (TSLP) is highly expressed in...

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Autores principales:	Leonie Wallmeyer, Kristina Dietert, Michaela Sochorová, Achim D. Gruber, Burkhard Kleuser, Kateřina Vávrová, Sarah Hedtrich
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/29bafae408b546e38cc4fe0bf4395f17
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spelling	oai:doaj.org-article:29bafae408b546e38cc4fe0bf4395f172021-12-02T15:18:54ZTSLP is a direct trigger for T cell migration in filaggrin-deficient skin equivalents10.1038/s41598-017-00670-22045-2322https://doaj.org/article/29bafae408b546e38cc4fe0bf4395f172017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00670-2https://doaj.org/toc/2045-2322Abstract Mutations in the gene encoding for filaggrin (FLG) are major predisposing factors for atopic dermatitis (AD). Besides genetic predisposition, immunological dysregulations considerably contribute to its pathophysiology. For example, thymic stromal lymphopoietin (TSLP) is highly expressed in lesional atopic skin and significantly contributes to the pathogenesis of AD by activating dendritic cells that then initiate downstream effects on, for example, T cells. However, little is known about the direct interplay between TSLP, filaggrin-deficient skin and other immune cells such as T lymphocytes. In the present study, FLG knockdown skin equivalents, characterised by intrinsically high TSLP levels, were exposed to activated CD4+ T cells. T cell exposure resulted in an inflammatory phenotype of the skin equivalents. Furthermore, a distinct shift from a Th1/Th17 to a Th2/Th22 profile was observed following exposure of T cells to filaggrin-deficient skin equivalents. Interestingly, TSLP directly stimulated T cell migration exclusively in filaggrin-deficient skin equivalents even in the absence of dendritic cells, indicating a hitherto unknown role of TSLP in the pathogenesis of AD.Leonie WallmeyerKristina DietertMichaela SochorováAchim D. GruberBurkhard KleuserKateřina VávrováSarah HedtrichNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Leonie Wallmeyer Kristina Dietert Michaela Sochorová Achim D. Gruber Burkhard Kleuser Kateřina Vávrová Sarah Hedtrich TSLP is a direct trigger for T cell migration in filaggrin-deficient skin equivalents
description	Abstract Mutations in the gene encoding for filaggrin (FLG) are major predisposing factors for atopic dermatitis (AD). Besides genetic predisposition, immunological dysregulations considerably contribute to its pathophysiology. For example, thymic stromal lymphopoietin (TSLP) is highly expressed in lesional atopic skin and significantly contributes to the pathogenesis of AD by activating dendritic cells that then initiate downstream effects on, for example, T cells. However, little is known about the direct interplay between TSLP, filaggrin-deficient skin and other immune cells such as T lymphocytes. In the present study, FLG knockdown skin equivalents, characterised by intrinsically high TSLP levels, were exposed to activated CD4+ T cells. T cell exposure resulted in an inflammatory phenotype of the skin equivalents. Furthermore, a distinct shift from a Th1/Th17 to a Th2/Th22 profile was observed following exposure of T cells to filaggrin-deficient skin equivalents. Interestingly, TSLP directly stimulated T cell migration exclusively in filaggrin-deficient skin equivalents even in the absence of dendritic cells, indicating a hitherto unknown role of TSLP in the pathogenesis of AD.
format	article
author	Leonie Wallmeyer Kristina Dietert Michaela Sochorová Achim D. Gruber Burkhard Kleuser Kateřina Vávrová Sarah Hedtrich
author_facet	Leonie Wallmeyer Kristina Dietert Michaela Sochorová Achim D. Gruber Burkhard Kleuser Kateřina Vávrová Sarah Hedtrich
author_sort	Leonie Wallmeyer
title	TSLP is a direct trigger for T cell migration in filaggrin-deficient skin equivalents
title_short	TSLP is a direct trigger for T cell migration in filaggrin-deficient skin equivalents
title_full	TSLP is a direct trigger for T cell migration in filaggrin-deficient skin equivalents
title_fullStr	TSLP is a direct trigger for T cell migration in filaggrin-deficient skin equivalents
title_full_unstemmed	TSLP is a direct trigger for T cell migration in filaggrin-deficient skin equivalents
title_sort	tslp is a direct trigger for t cell migration in filaggrin-deficient skin equivalents
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/29bafae408b546e38cc4fe0bf4395f17
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TSLP is a direct trigger for T cell migration in filaggrin-deficient skin equivalents

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