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| Item Type: | Article |
|---|---|
| Title: | TSLP is a direct trigger for T cell migration in filaggrin-deficient skin equivalents |
| Creators Name: | Wallmeyer, L. and Dietert, K. and Sochorová, M. and Gruber, A.D. and Kleuser, B. and Vávrová, K. and Hedtrich, S. |
| 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. |
| Keywords: | CD4-Positive T-Lymphocytes, Cell Movement, Cytokines, Dendritic Cells, Filaggrin Proteins, Gene Expression, Intermediate Filament Proteins, Lipid Metabolism, Lymphocyte Activation, Skin, T-Lymphocyte Subsets, Th1 Cells, Th17 Cells, Th2 Cells, Thymic Stromal Lymphopoietin, Tight Junction Proteins |
| Source: | Scientific Reports |
| ISSN: | 2045-2322 |
| Publisher: | Nature Publishing Group |
| Volume: | 7 |
| Number: | 1 |
| Page Range: | 774 |
| Date: | 4 April 2017 |
| Official Publication: | https://doi.org/10.1038/s41598-017-00670-2 |
| External Fulltext: | View full text on PubMed Central |
| PubMed: | View item in PubMed |
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