Mechanisms of T-cell homing to skin.

Although many individual components of the lymphocyte's migratory machinery have been identified and analyzed for function in vitro, interesting questions remain regarding the in vivo integration of these components. How does the lymphocyte "choose" a direction for migration in the complex cytokine/chemokine environment of inflamed dermis when multiple chemokines secreted by multiple cell types are present? Can differences in chemokine expression explain the clinical and histologic differences seen in different inflammatory skin disease? What are the roles of proteins such as VAP-1? Our present understanding of lymphocyte migration has already led to the use of monoclonal antibodies to integrins such as LFA-1 that can potentially be of therapeutic use in skin diseases such as psoriasis. Small molecule inhibitors of T lymphocyte-specific receptors such as CCR4 or CXCR3 are promising agents for controlling T cell-mediated inflammation but have yet to be developed. These receptors may have greater selective expression on skin-homing T cells and thus may decrease the risk of iatrogenic immunosuppression. Close cooperation between the pharmaceutical industry and basic scientists will hopefully lead to the evolution of such compounds and toward more effective treatment of inflammatory skin diseases.