Psoriasis is an inflammatory skin disease affecting 2-3% of the general population and whose precise aetiology remains poorly understood. Several lines of evidence suggest that the nuclear receptor peroxisome proliferator activator (PPAR) β/δ, known to regulate epithelial differentiation, proliferation, wound healing and epidermal barrier recovery, contributes to psoriasis pathogenesis. It is unclear, however, whether activation of PPAR β/δ is sufficient to trigger psoriasis-like inflammation.
Overexpression of PPARβ/δ in keratinocytes in mice leads to death 8 days after birth despite food intake and integrity of the skin barrier. The reason of lethality remains to be elucidated. K14PPARβ/δ Tg mice developed inflammatory cutaneous lesions 5 days after birth, that worsened with time. These skin lesions shared similar clinical, histological and immunological features with human psoriasis. However, some disparities with human lesions were observed such as for some cytokine (IL-4, IL-33) mRNA profiles and immunologic responses. T-cells, commonly found in psoriasis lesions, were rare in skin of K14PPARβ/δ Tg mice, probably as a consequence of an immature immune system at 5 days of life. Microarray analysis showed a similar transcript profile in K14PPARβ/δ Tg mice compared to human psoriasis. Though K14PPARβ/δ Tg mice may represent an interesting experimental model to better understand the pathophysiology of the early stages of human psoriasis.

Psoriasis-like inflammation in K14PPARβ/δ transgenic mice selectively overexpressing PPARβ/δ in keratinocytes.