Targeting TREX2: an innovative keratinocyte-based therapy for psoriasis and atopic dermatitis

[spa] The fact that TREX2 is specifically expressed on KCs, upregulated in psoriatic skin and its loss leads to a decreased inflammation in mice models of the disease, points TREX2 as a candidate target for new KC-based PsO therapies. We hypothesize that the inhibition of TREX2 can be as effective as the most advanced available treatments, which mainly target the immune system, while avoiding their adverse broad immunosuppressive effects. Therefore, blocking TREX2 activity could be a promising non-immune and skin-specific approach to diminish KC-derived inflammation and avert the adverse side-effects associated to systemic treatments targeting the immune system. In this context, the global aim of the present PhD thesis was to identify, develop and characterize specific and effective TREX2 inhibitory compounds for PsO treatment and other TREX2-driven diseases and further determine their suitability and efficacy for future clinical trials. The specific goals were: 1. To identify and characterize specific, selective, potent and safe TREX2 inhibitory compounds to treat PsO. 2. To evaluate the role of TREX2 in AD and as therapeutic target in this disease. 3. To characterize the molecular mechanisms of TREX2 inhibitors.