Activation of Wnt5A signaling is required for CXC chemokine ligand 12–mediated T-cell migration
AUTOR(ES)
Ghosh, Manik C.
FONTE
American Society of Hematology
RESUMO
Chemokines mediate the signaling and migration of T cells, but little is known about the transcriptional events involved therein. Microarray analysis of CXC chemokine ligand (CXCL) 12−treated T cells revealed that Wnt ligands are significantly up-regulated during CXCL12 treatment. Real-time polymerase chain reaction and Western blot analysis confirmed that the expression of noncanonical Wnt pathway members (eg, Wnt5A) was specifically up-regulated during CXCL12 stimulation, whereas β-catenin and canonical Wnt family members were selectively down-regulated. Wnt5A augmented signaling through the CXCL12-CXCR4 axis via the activation of protein kinase C. Moreover, Wnt5A expression was required for CXCL12–mediated T-cell migration, and rWnt5A sensitized human T cells to CXCL12-induced migration. Furthermore, Wnt5A expression was also required for the sustained expression of CXCR4. These results were further supported in vivo using EL4 thymoma metastasis as a model of T-cell migration. Together, these data demonstrate that Wnt5A is a critical mediator of CXCL12-CXCR4 signaling and migration in human and murine T cells.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2727408Documentos Relacionados
- T-Cell lymphoma model for the analysis of interleukin 1-mediated T-cell activation.
- T-cell activation is required for efficient replication of human herpesvirus 6.
- T-cell activation by the CD28 ligand B7 is required for cardiac allograft rejection in vivo.
- A functional T-cell receptor signaling pathway is required for p95vav activity.
- Inhibition of T-cell antigen receptor-mediated transmembrane signaling by protein kinase C activation.