Our long term objective is to understand the mechanisms through which the epidermis maintains balanced growth. Recent associations between skin and cells of the immune system (eg. lymphocytes, macrophages, and epidermal Langerhans cells) and the ability of epidermal cells to secrete lymphokine-like molecules suggested to us that other similarities between lymphoid interactions and epidermal interactions might also occur. This grant proposal arises from our discovery that a sub-population of epidermal cells expresses Thy1 antigen (Thy1+ cells) and such populations can be detected in frozen sections and epidermal whole mounts from in vivo skin and are also present in epidermal cell cultures. We hypothesize that Thy1+ cells may play regulatory roles in the processes of cell proliferation, differentiation and defense, central to the maintenance of epidermal homeostasis. The specific objective of this proposal is to study relationships between Thy1+ cells and directed perturbations of in vivo skin and in vitro epidermal culture systems in order to associate Thy1+ cells with epidermal function. Studies of the topological distribution of epidermal Thy1+ cells allow for correlation of their relative abundance within areas of skin and epithelium which differ functionally and specifically in patterns of differentiation, tissue type, antigenic load and degree of trauma. Skin will be stimulated chemically by the mitogen TPA or physically, by tape stripping and the behavior of Thy1+ cells will be followed by immunofluorescence microscopy. Epidermal cell culture systems will be used to study endogenous Thy1 protein synthesis and the response of Thy1+ cells to a series of biologic response modifiers eg. TPA, EGF, cyclic AMP etc., known to affect the epidermis. Cultures will be depleted of Thy1+ cells to study the contribution of these cells to the endogenous regulation of these cultures (eg. Can Thy1 cells be associated with ETAF production?). Emphasis will be placed on potential regulatory interactions between Thy1+ cells and Langerhans cells. Thus, having made the observation of Thy1 expression by a sub-population of epidermal cells, this proposal will examine whether these cells can be associated with particular epidermal responses. Successful completion of this work will lead directly to examination of the molecular mechanisms through which such cells elicit these responses and how such mechanisms are altered in disease.
