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    TSLP is a direct trigger for T cell migration in filaggrin-deficient skin equivalents (2017)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Wallmeyer, Leonie (WE 12)
    Dietert, Kristina (WE 12)
    Sochorová, Michaela (WE 12)
    Gruber, Achim D (WE 12)
    Kleuser, Burkhard (WE 12)
    Vávrová, Kateřina (WE 12)
    Hedtrich, Sarah (WE 12)
    Quelle
    Scientific reports
    Bandzählung: 7
    Heftzählung: 1
    Seiten: 774
    ISSN: 2045-2322
    Sprache
    Englisch
    Verweise
    DOI: 10.1038/s41598-017-00670-2
    Pubmed: 28377574
    Kontakt
    Institut für Tierpathologie

    Robert-von-Ostertag-Str. 15
    14163 Berlin
    +49 30 838 62450
    pathologie@vetmed.fu-berlin.de

    Abstract / Zusammenfassung

    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.