Uncontrolled sclerosis can functionally incapacitate any organ system, yet little is known about its phatophysiology(s). Using as a model the cutaneous sclerosis seen in murine graft-vs-host disease (GVHD), the proposal will examine in vitro several cellular interactions, as a first step toward a better understanding of the in vivo events that eventuate in collagen accumulation. We will use two murine chimeras: a chimera that spontaneously develops sclerosis during the second phase of its GVHD; and a chimera that normally doesn't develop sclerosis during GVHD, but that does sclerose selectively in ultraviolet light-exposed skin. We will measure collagen synthesis in fibroblast cultures, under conditions that should begin to clarify what cellular interactions are important. Future work will be centered on more precisely identifying the mediators of sclerosis and on designing drug therapies appropriate for each stage of the pathogenetic process.
