Cutting edge: differential requirements for Stat4 in expression of glycosyltransferases responsible for selectin ligand formation in Th1 cells

J Immunol. 2001 Jul 15;167(2):628-31. doi: 10.4049/jimmunol.167.2.628.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Fucosyltransferases / biosynthesis
  • Fucosyltransferases / physiology
  • Ligands
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • N-Acetylglucosaminyltransferases / biosynthesis*
  • N-Acetylglucosaminyltransferases / physiology
  • STAT4 Transcription Factor
  • Selectins / biosynthesis
  • Selectins / metabolism*
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • Th1 Cells / enzymology*
  • Th1 Cells / metabolism
  • Trans-Activators / deficiency
  • Trans-Activators / genetics
  • Trans-Activators / physiology*

Substances

  • DNA-Binding Proteins
  • Ligands
  • STAT4 Transcription Factor
  • Selectins
  • Stat4 protein, mouse
  • Trans-Activators
  • Fucosyltransferases
  • N-Acetylglucosaminyltransferases
  • beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-acetylglucosaminyl transferase
  • galactoside 3-fucosyltransferase