Preclinical skin models closely mimicking inflammatory features in diseased skin, such as psoriasis, are needed
to support the development of anti-inflammatory drugs in dermatology. Approaches based on the incorporation of
immune cells in reconstructed skin models are now developed. However, these skin models lack tissue
complexity and diversity of immune cells and show an incomplete skin barrier function.
To overcome these issues, we have developed and characterized a T cell-driven skin inflammation model based
on the NativeSkin® explant technology. In our approach we intradermally injected anti-CD3 and -CD28 antibodies
to promote in situ activation of resident T cells. Skin models were then cultured up to 7 days with a chemicallydefined
culture medium supplemented with IL-1b, IL-23 and TGF-β to induce Th17/Th1 T cell polarization.
Histological analysis of the inflamed skin model showed characteristic changes in the epidermis in contrast to
non-inflamed skin models. Analysis of cytokine levels in culture media at days 4 and 7 showed sustained
secretion of IL-17A, IL-22, IFN-γ and TNF-α as well as lack of IL-4 expression, supporting successful activation
and differentiation of Th17/Th1 cells. Furthermore, secretion of T cell cytokines resulted in epidermal activation
shown by over-expression of S100A7 and Keratin 16.
Finally, pharmacological responses in the model were evaluated both in a therapeutic and prophylactic setting by
once daily topical application of a PDE-4 inhibitor or betamethasone dipropionate. Results showed that both
compounds and treatment settings led to strong reduction in secretion of inflammatory cytokines, restoration or
preservation of epidermal integrity and viability, indicating anti-inflammatory effects.
In conclusion, we developed a new fully human ex vivo skin model that successfully reproduces key features of
skin inflammation observed in psoriatic lesions and showed the use of this model to assess efficacy of topically
applied test compounds.

Evaluation of pharmacological responses in a fully human ex vivo skin model following in situ T cell activation with Th17 / Th1 psoriasis-like phenotype