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.
- MeSH
- aktivace lymfocytů MeSH
- buňky Th17 imunologie metabolismus MeSH
- CD4-pozitivní T-lymfocyty imunologie metabolismus MeSH
- cytokiny metabolismus MeSH
- dendritické buňky imunologie metabolismus MeSH
- exprese genu MeSH
- kůže imunologie metabolismus MeSH
- lidé MeSH
- metabolismus lipidů MeSH
- pohyb buněk imunologie MeSH
- proteiny intermediálních filament nedostatek MeSH
- proteiny těsného spoje genetika metabolismus MeSH
- T-lymfocyty - podskupiny imunologie metabolismus MeSH
- Th1 buňky imunologie metabolismus MeSH
- Th2 buňky imunologie metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH