Wnt signaling induces matrix metalloproteinase expression and regulates T cell transmigration.
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.
Wu
Beibei
B
Center for Immunology, Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, CA 92697, USA.
Crampton
Steve P
SP
Hughes
Christopher C W
CC
D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D051157:Frizzled Receptors / Q000276:immunology / Q000378:metabolism; D006801:Humans; D053504:Matrix Metalloproteinases, Membrane-Associated / Q000096:biosynthesis* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection; D051153:Wnt Proteins / Q000276:immunology / Q000378:metabolism*
D051157:Frizzled Receptors; D051153:Wnt Proteins; D053504:Matrix Metalloproteinases, Membrane-Associated