Cutting edge: differential requirements for Stat4 in expression of glycosyltransferases responsible for selectin ligand formation in Th1 cells.
A role for Stat4 in IL-12-induced up-regulation of selectin ligands on Th1 cells was explored. Th1 cells generated from Stat4(-/-) mice exhibited no IL-12-inducible P-selectin ligands, no up-regulation of core 2 beta1,6-glucosaminyltransferase I (C2GlcNAcT-I), and low levels of the Th1 transcription factor T-bet. In contrast, Stat4(-/-) Th1 cells exhibited only a partial defect in expression of IL-12-inducible E-selectin ligands and expressed equivalently high levels of alpha1,3-fucosyltransferase VII (FucT-VII) as wild-type Th1 cells. FucT-VII expression was induced by T cell activation, and was enhanced by IL-12 independently of Stat4, whereas C2GlcNAcT-I up-regulation was mediated exclusively by IL-12, acting through Stat4. These data show that FucT-VII and C2GlcNAcT-I are controlled through distinct pathways and imply the existence of at least one other IL-12-inducible glycosyltransferase required for E-selectin and possibly P-selectin ligand formation in Th1 cells.
White
S J
SJ
Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, IL 60611, USA.
Underhill
G H
GH
Kaplan
M H
MH
Kansas
G S
GS
D000818:Animals; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005647:Fucosyltransferases / Q000096:biosynthesis / Q000502:physiology; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D017351:N-Acetylglucosaminyltransferases / Q000096:biosynthesis* / Q000502:physiology; D050797:STAT4 Transcription Factor; D019087:Selectins / Q000096:biosynthesis / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D018417:Th1 Cells / Q000201:enzymology* / Q000378:metabolism; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D004268:DNA-Binding Proteins; D008024:Ligands; D050797:STAT4 Transcription Factor; D019087:Selectins; C494091:Stat4 protein, mouse; D015534:Trans-Activators; D005647:Fucosyltransferases; D017351:N-Acetylglucosaminyltransferases; C053024:beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-acetylglucosaminyl transferase; C031692:galactoside 3-fucosyltransferase