title: 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 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.
authors.affiliation: Institute for Pharmacy, Pharmacology and Toxicology, Freie Universität Berlin, Berlin, Germany.
authors.forename: Leonie
authors.initials: L
authors.lastname: Wallmeyer
authors.affiliation: Department of Veterinary Medicine, Institute of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Dietert
authors.affiliation: Faculty of Pharmacy, Charles University Prague, Hradec Kralove, Czech Republic.
authors.forename: Michaela
authors.initials: M
authors.lastname: Sochorová
authors.affiliation: Department of Veterinary Medicine, Institute of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany.
authors.forename: Achim D
authors.initials: AD
authors.lastname: Gruber
authors.affiliation: Institute of Nutritional Science, Department of Toxicology, University of Potsdam, Potsdam, Germany.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Kleuser
authors.affiliation: Faculty of Pharmacy, Charles University Prague, Hradec Kralove, Czech Republic.
authors.forename: Kateřina
authors.identifier: http://orcid.org/0000-0002-8502-4372
authors.initials: K
authors.lastname: Vávrová
authors.affiliation: Institute for Pharmacy, Pharmacology and Toxicology, Freie Universität Berlin, Berlin, Germany. sarah.hedtrich@fu-berlin.de.
authors.forename: Sarah
authors.identifier: http://orcid.org/0000-0001-6770-3657
authors.initials: S
authors.lastname: Hedtrich
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D000091344:Filaggrin Proteins; D015870:Gene Expression; D006801:Humans; D007381:Intermediate Filament Proteins / Q000172:deficiency*; D050356:Lipid Metabolism; D008213:Lymphocyte Activation; D012867:Skin / Q000276:immunology* / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D062725:Tight Junction Proteins / Q000235:genetics / Q000378:metabolism; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D062725:Tight Junction Proteins; D000094632:Thymic Stromal Lymphopoietin