T-cell dynamics of inflammatory skin diseases.
The migration of memory T-cells to sites of inflammation is a multistep process controlled by an array of specific receptor-ligand pairs. Chemokines and their receptors represent a central paradigm of the molecular basis of the skin-homing of T-cells. Although CCR4 and CCR10 are both associated with conventionally defined skin-homing T-cells, the association is not necessarily perfect. Interaction between E-selectin and its ligand may represent more specific targets for therapeutic intervention. Although fucosyl transferase?VII is essential for generating E-selectin ligands necessary for T-cell homing to skin, fucosyltransferase-IV, another fucosyltransferase expressed to a significant degree in T-cells, can also generate E-selectin ligands. The induction and upregulation of both enzymes can be co-ordinately regulated depending on their state of activation and differentiation and the cytokine milieu. The dynamic balance between the two enzymes is a major check point for the regulation of skin-homing T-cell differentiation. Polarized T-cells regulate their adhesions on a minute-to-minute basis depending on the cytokine environment. Soluble adhesion molecules found to be increased in chronic inflammatory skin diseases may serve to limit the duration or magnitude of T-cell recruitment. In addition to T-cells migrating from the circulation, T-cells indigenously residing in the tissue itself, such as skin-resident T-cells, would also be responsible for tissue damage. It should also be appreciated that T-cell recruitment to the skin is critical for host defense and that no definitive means exist to distinguish protective regulatory T-cells from pathogenic T-cells.
Shiohara
Tetsuo
T
Department of Dermatology Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan. tpshio@kyorin-u.ac.jp
Mizukawa
Yoshiko
Y
Hayakawa
Jun
J
Hayakawa
Kazuhito
K