Immune responses in the skin are mediated by effector T cells migrating to the inflamed and injured area. Inhibition of this migration has long been an attractive, though challenging, basis for anti-inflammatory treatment strategies. The migration is regulated, in part, by the proteins E-selectin and P-selectin present within endothelial cells of the skin. In a new study, Charles Dimitroff and colleagues from Harvard Medical School introduce a new strategy for the inhibition of selectin ligand production, which blocks E-selectin ligand expression and therefore ultimately prevents the development of contact hypersensitivity (CHS) responses. Most interestingly, the agent used – a novel fluorosugar compound, 4-F-GlcNAc -– inhibited CHS responses with higher efficacy than glucocorticoids or calcineurin inhibitors currently available for the treatment of allergic skin reactions such as psoriasis and atopic dermatitis. The authors indicate that while a novel drug may still be some way off in terms of an available treatment, inhibition of selectin ligand activity has the potential for efficacy in both preventative and therapeutic applications. In an accompanying commentary, Thomas Zollner and Khusru Asadullah from Schering AG in Berlin, Germany, discuss the underlying mechanisms of this approach and potential therapeutic applications.
TITLE: Prevention of leukocyte migration to inflamed skin with a novel fluorosugar modifier of cutaneous lymphocyte-associated antigen
AUTHOR CONTACT: Charles J. Dimitroff Harvard Institutes of Medicine, Boston, Massachusetts, USA. Phone: 617-525-5602 Fax: 617-525-5571 Email: email@example.com