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