Differential regulation and impact of fucosyltransferase VII and core 2 β1,6‐ N ‐acetyl‐glycosaminyltransferase for generation of E ‐selectin and P ‐selectin ligands in murine CD 4 + T cells

Summary Ligands for E ‐selectin and P ‐selectin ( E ‐lig and P ‐lig) are induced on CD 4 + T cells upon differentiation into effector T cells. Glycosyltransferases, especially α 1,3‐fucosyltransferase VII ( F uc T ‐VII) and core 2 β1,6‐ N ‐acetyl‐glycosaminyltransferase I ( C 2 G lc NA c T ‐I), are critical for their synthesis. We here analysed the signals that control the expression of E ‐lig, P ‐lig and m RNA coding for F uc T ‐VII and C 2 G lc NA c T ‐I. In line with previous reports, we found that P‐lig expression correlates with the regulation of C 2 G lc NA c T ‐I, whereas E ‐lig expression can occur at low levels of C 2 G lc NA c T ‐I m RNA but requires high F uc T ‐VII m RNA expression. Interestingly, the two enzymes are regulated by different signals. Activation‐induced C 2 G lc NA c T ‐I up‐regulation under permissive (T helper type 1) conditions was strongly reduced by cyclosporin A ( C s A ), suggesting the involvement of T ‐cell receptor‐dependent, calcineurin/ NFAT ‐dependent signals in combination with interleukin‐12 ( IL ‐12) ‐mediated signals in the regulation of C 2 G lc NA c T ‐I. In contrast, expression of F uc T ‐VII m RNA was not significantly inhibited by C s A . Interleukin‐4 inhibited the expression of F uc T ‐VII but IL ‐2 and IL ‐7 were found to support induction of F uc T ‐VII and E ‐lig. E ‐selectin, P ‐selectin and their ligands initially appeared to have rather overlapping functions. These findings however, unravel striking differences in the regulation of E ‐lig and P ‐lig expression, dictated by the dominance of F uc T ‐VII and C 2 G lc NA c T ‐I, respectively, and their dependency on signals from either promiscuous or homeostatic cytokines ( F uc T ‐VII) or a strong T ‐cell receptor signal in combination with inflammatory cytokines in case of C 2 G lc NA c T ‐I.