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 skin, is dependent on T cell expression of ligands for the endothelial selectins. Underlying expression of these ligands is the expression of alpha(1,3)-fucosyltransferase VII (FucT-VII), a FucT essential for biosynthesis 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 functional selectin ligands have not been identified, and are likely to be important 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-beta1 as able to up-regulate FucT-VII mRNA levels and selectin ligands on activated 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 selective ability of TGF-beta1 to induce selectin ligands on activated T cells is likely important for T cell homing to the gut, which is a strongly selectin-dependent site, and correlates with the ability of TGF-beta1 to coordinately induce other gut-associated homing pathways.
Wagers
A J
AJ
Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, IL 60611, USA.
Kansas
G S
GS
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology* / Q000276:immunology* / Q000502:physiology; D016466:CHO Cells; D002448:Cell Adhesion / Q000276:immunology; D002478:Cells, Cultured; D006224:Cricetinae; D019040:E-Selectin / Q000378:metabolism / Q000502:physiology; D004790:Enzyme Induction / Q000276:immunology; D005647:Fucosyltransferases / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007156:Immunologic Memory; D008024:Ligands; D008213:Lymphocyte Activation / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000276:immunology*; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D017351:N-Acetylglucosaminyltransferases / Q000096:biosynthesis / Q000235:genetics; D019007:P-Selectin / Q000378:metabolism / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D016212:Transforming Growth Factor beta / Q000502:physiology*; D015854:Up-Regulation / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases
D019040:E-Selectin; D008024:Ligands; D019007:P-Selectin; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D005647:Fucosyltransferases; D017351:N-Acetylglucosaminyltransferases; C053024:beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-acetylglucosaminyl transferase; C031692:galactoside 3-fucosyltransferase; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases