Up-regulation of
vascular endothelial growth factor (
VEGF) plays a primary role in the pathogenesis of
psoriasis. Transgenic mice over-expressing
VEGF under the
Keratin 14 (K14) promoter develop an inflammatory skin condition with many of the pathobiological features of human
psoriasis. In this work, the development of spontaneous psoriatic-like
dermatitis in K14-VEGF transgenic mice was monitored from week 6 to week 44 and skin lesions were characterized clinically (application of a clinical score system comparable to the human
Psoriasis Area and Severity Index), microscopically (histopathology, leukocyte subset and neoangiogensis) and immunologically (evaluation of local and systemic
cytokine/
chemokine profiles). Based on PASI score system, three progressive clinical phases were identified: mild acute (8-14 weeks of age), moderate subacute (15-21 weeks of age) and severe chronic-active (22-44 weeks of age)
dermatitis. Microscopically, skin lesions consisted of progressive proliferative psoriatic-like
dermatitis dominated by dermo-epidermal infiltrates of CD3-positive lymphocytes, an increased number of mast cells and neoangiogenesis. Both local and systemic up-regulation of pro-inflammatory (IL-12, TNF-alpha, IL-6, MCP-1 and IL-8) and regulatory (IL-10)
cytokines/
chemokines was observed, mainly during the later stages of disease development. The results obtained in this study further confirm the central role of
VEGF over-expression in the development of psoriatic-like
dermatitis. Similarly to what is reported for human
psoriasis, both the local and systemic immunologic profiles observed in K14-VEGF transgenic mice suggest that a combined Th1 and Th17 response may be implicated in lesion development. The identification of three progressive stages of disease, each with peculiar clinicopathological features, renders the K14-VEGF transgenic mouse a valuable model to study novel
immunotherapies for
psoriasis.