The broad objective remains: The etiology of psoriasis. The basic hypothesis to be tested states that because baseline epidermal proliferation is altered in skin of patients with psoriasis, there is a cellular based message system within the skin that permits/causes the altered epidermal proliferation. The major specific aims are to define this cellular component. First, is the abnormal cellular component causative to the epidermal hyperproliferation of psoriasis within the epidermis (epidermal cells or Langerhans cells), the dermis (fibroblasts, endothelial cells, mast cells, or Ia+ cells), or are all components necessary? Second, does the abnormal but equal hyperproliferation of the epidermis of skin grafts from involved and uninvolved sites of psoriasis to nude mice graduallly correct with prolonged times of engraftment? If correction does occur, what are the cellular changes and parameters which defined this phenomenon? The methodology to approach the goal of defining those cellular components important to the hyperproliferation of the epidermis of patients with psoriasis involves an artificial dermis containing and supporting specific cell types. The artificial dermis will support the proliferation and differentiation of various epidermal combinations, epidermal sheets or epidermal cell suspensions, from normal and psoriatic subjects, when transplanted to the nude mouse. Epidermal sheets maintained on this artificial dermis appear to be devoid of Langerhans cells. This artificial dermis can also be impregnated with fibroblasts from normal and psoriatic subjects. Dermal fragments can be placed under this thin, but very porous, membrane, and the effects of various dermal types on epidermal proliferation/differentiation determined. The read-out system includes those changes in epidermal proliferation and morphologic changes in the stratum corneum secondary to experimental manipulations, comparing normal with psoriatic. Experimental manipulations include defined cell type on or in the artificial dermis and the response of these skin equivalents of defined cell types to proliferative stimuli. Conclusions as to the cell/ tissue causative to hyperproliferation of the epidermis of psoriasis will be based upon depletion and reconstitution experiments, normal vs. psoriasis.
