Potent induction of alpha(1,3)-fucosyltransferase VII in activated CD4(+) T cells by TGF-beta 1 through a p38 mitogen-activated protein kinase-dependent pathway

Homing of effector T cells to sites of inflammation, particularly in the sk in, is dependent on T cell expression of ligands for the endothelial select ins. Underlying expression of these ligands is the expression of alpha>(*) over bar * (1,3)-fucosyltransferase VII (FucT-VII), a FucT essential for bi osynthesis of selectin ligands, FucT-VII is sharply induced in activated T cells by IL-12, but cytokines other than IL-12 that induce FucT-VII and fun ctional selectin ligands have not been identified, and are likely to be imp ortant in homing of T cells to other selectin-dependent sites, Screening of a number of cytokines known to be active on T cells identified only TGF-be ta1 as able to up-regulate FucT-VII mRNA levels and selectin ligands on act ivated CD4 T cells. The sharp increase in FucT-VII induced by TGF-beta1 in activated T cells was completely blocked by pharmacologic inhibition of p38 mitogen-activated protein kinase, but was unaffected by mitogen-activated protein/extracellular signal-related kinase kinase inhibitors. The selectiv e ability of TGF-beta1 to induce selectin ligands on activated T cells is l ikely important for T cell homing to the gut, which is a strongly selectin- dependent, site, and correlates with the ability of TGF-beta1 to coordinate ly induce other gut-associated homing pathways.