Laboratory for Investigative Dermatology

James G. Krueger
D. Martin Carter Professor in Clinical Investigation

The focus of this group is on the biology of epithelial cells and on the study of psoriasis, as a model autoimmune disease.

Psoriasis is a common, painful, and disabling skin disease defined by epithelial cell hyperplasia, altered differentiation of the epidermis, and tissue infiltration by activated T-lymphocytes. Over the last several years we have identified a number of growth factor/cytokine pathways that can explain activation of diverse cell types within psoriatic lesions, and many of these factors link inflammation with the epithelial cell proliferative response. As there are no animal models of psoriasis, we have studied the pathogenesis of psoriasis in patients within the Rockefeller University Hospital using approaches ranging from identification of genes activated or suppressed in psoriatic skin by PCR-based differential displays and gene cloning to pharmacological studies of cellular suppression in diseased tissue. During the last year we have been using a specific lymphocyte toxin (a fusion protein between IL-2 and diphtheria toxin, "DAB389IL-2") to investigate the contribution of activated T-lymphocytes to psoriasis pathogenesis. Our results suggest that psoriasis is induced by the action of tissue-infiltrating T-lymphocytes (probably the CD8+ subset) which trigger keratinocytes into a physiologically regulated wound repair pathway of hyperplasia and altered differentiation. We will be continuing to characterize lymphocyte-keratinocyte interactions in psoriasis, with the view of elucidating the "autoimmune" basis of this disorder. Clinically based studies will continue to investigate different novel approaches to target T-lymphocyte depletion from psoriatic tissue. We will also be continuing our basic studies of cellular and molecular pathogenesis, with concentration on identification of genes regulating proliferation, differentiation, and inflammation within skin.