Figure 5. RDD gene therapy reduces cutaneous vascularization and alleviates psoriasis in human skin transplanted onto immunodeficient mice.

(A) Psoriatic skin with a full-fledged phenotype was transplanted onto Prkdc^scid mice, and recipient mice were either left untreated (representative of n = 12 mice) or subjected to gene therapy with pVAX-RFP (representative of n = 14 mice) or pVAX-RDD (representative of n = 13 mice). The macroscopic aspect of the blood vessels on the underside of the skin transplants demonstrates that gene therapy with RDD reduces cutaneous vascularization. Original magnification, ~×3. (B) Transplanted psoriatic skin was analyzed by immunohistochemistry using the indicated reagents detecting blood vessels. Somatic gene therapy with pVAX-RDD results in reduction of both number and size of cutaneous blood vessels as compared with that of the controls. Blood vessels of human (CD31 and SMA) as well as murine (BS-1) origin are affected. Scale bar: 50 μm. (C) Transplants of fully developed psoriasis transplanted onto Prkdc^scid mice were further analyzed by staining with H&E (left panels) or by immunohistochemistry using the indicated antibodies detecting proliferating cells (Ki67) or T cells (CD3). Both the epidermal thickness and the number of proliferating epidermal keratinocytes are reduced in transplants from mice treated by RDD gene therapy. Scale bar: 50 μm. (D) Quantitative morphometric analysis of transplants from Prkdc^scid mice. The top graph depicts the epidermal thickness as determined by blinded measurements. The bottom graph shows the number of proliferating epidermal cells in mice subjected to RDD gene therapy compared with that of the controls. Values represent mean ± SD. ***P < 0.001.