Genoskin recently developed InflammaSkin®, a T cell-driven skin inflammation model for psoriasis based on the activation and differentiation into a Th17/Th1 phenotype of skin resident T cells. This ex vivo human skin model is composed of epidermis and dermis with or without the underlying subcutaneous tissue. In the presence of the adipose tissue, it is designed to support subcutaneous delivery of therapeutic compounds. 
T-cell activation and differentiation in InflammaSkin® with or without adipose tissue, led to a strong upregulation of the release of IL-17A, IL-22, IL-27 and IFNγ pro-inflammatory cytokines after 3- and 7-days culture, as well as an important loss of tissue integrity and cell viability at the histological level. Release of T cell-derived cytokines also led to overexpression of S100A7 and Keratin 16 epidermal activation marker. 
In order to assess pharmacological response of the model to subcutaneous administration of biologics, adalimumab was injected in the fat tissue layer of the model after 3 days of in situ activation and polarization of resident T-cells. 
Histological analysis showed improvement of skin cells viability and partial restoration of skin structure 4 days after adalimumab delivery, as well as a strong decrease in S100A7 and keratin 16 expression in the epidermis suprabasal layers. Furthermore, analysis of cytokine levels in culture media showed dose-dependent downregulation of IL-17A, IL-22 and IFNγ but not IL-27 release, indicating anti-inflammatory effect of therapeutic treatment with adalimumab, a well-known anti-TNF immunosuppressive monoclonal antibody. 
In conclusion, we demonstrated that the InflammaSkin® model with adipose tissue successfully responds to subcutaneous injection of biologics and could become key to assess the efficacy of subcutaneously-delivered therapeutic compounds.

Evaluation of pharmacological responses to subcutaneous injection of adalimumab in InflammaSkin®, a full-thickness human ex vivo skin model reproducing key features of psoriatic lesions