Wnt signaling induces matrix metalloproteinase expression and regulates T cell transmigration

Immunity. 2007 Feb;26(2):227-39. doi: 10.1016/j.immuni.2006.12.007.

Abstract

Wnts are a family of secreted glycoproteins with diverse developmental roles, including regulation of cell migration; however, little is known about wnt signaling in mature T cells. We find that endothelial-cell-derived wnts, acting through Frizzled receptors, induce matrix metalloproteinase (MMP) 2 and MMP9 expression in effector T cells. Blocking wnt signaling, or MMP activity, reduces T cell migration through the basement membrane in vitro and into inflamed skin in vivo. Wnt signaling stabilizes beta-catenin protein in T cells and directly targets the MMP promoters through tandem TCF sites. Thus, our data support a necessary and previously unexpected role for wnt signaling in T cell extravasation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Chemotaxis, Leukocyte / immunology*
  • Endothelial Cells / metabolism
  • Female
  • Frizzled Receptors / immunology
  • Frizzled Receptors / metabolism
  • Humans
  • Matrix Metalloproteinases, Membrane-Associated / biosynthesis*
  • Matrix Metalloproteinases, Membrane-Associated / immunology
  • Mice
  • Mice, Inbred BALB C
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / immunology*
  • T-Lymphocytes / immunology*
  • Transfection
  • Wnt Proteins / immunology
  • Wnt Proteins / metabolism*

Substances

  • Frizzled Receptors
  • Wnt Proteins
  • Matrix Metalloproteinases, Membrane-Associated