title: Activation of Wnt5A signaling is required for CXC chemokine ligand 12-mediated T-cell migration.
abstract: 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 beta-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.
authors.affiliation: Laboratory of Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: Manik C
authors.initials: MC
authors.lastname: Ghosh
authors.forename: Gary D
authors.initials: GD
authors.lastname: Collins
authors.forename: Bolormaa
authors.initials: B
authors.lastname: Vandanmagsar
authors.forename: Kalpesh
authors.initials: K
authors.lastname: Patel
authors.forename: Margaret
authors.initials: M
authors.lastname: Brill
authors.forename: Arnell
authors.initials: A
authors.lastname: Carter
authors.forename: Ana
authors.initials: A
authors.lastname: Lustig
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Becker
authors.forename: William W
authors.initials: WW
authors.lastname: Wood
authors.forename: Chineye D
authors.initials: CD
authors.lastname: Emeche
authors.forename: Amanda D
authors.initials: AD
authors.lastname: French
authors.forename: Michael P
authors.initials: MP
authors.lastname: O'Connell
authors.forename: Mai
authors.initials: M
authors.lastname: Xu
authors.forename: Ashani T
authors.initials: AT
authors.lastname: Weeraratna
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Taub
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D054377:Chemokine CXCL12 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology; D051153:Wnt Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000071818:Wnt-5a Protein; D051176:beta Catenin / Q000235:genetics / Q000276:immunology
chemical_list: C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D011518:Proto-Oncogene Proteins; D019718:Receptors, CXCR4; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C438615:Wnt5a protein, mouse; D051176:beta Catenin