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PMID:19520808

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Citation

Ghosh, MC, Collins, GD, Vandanmagsar, B, Patel, K, Brill, M, Carter, A, Lustig, A, Becker, KG, Wood, WW 3rd, Emeche, CD, French, AD, O'Connell, MP, Xu, M, Weeraratna, AT and Taub, DD (2009) Activation of Wnt5A signaling is required for CXC chemokine ligand 12-mediated T-cell migration. Blood 114:1366-73

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.

Links

PubMed PMC2727408 Online version:10.1182/blood-2008-08-175869

Keywords

Animals; Cell Line, Tumor; Cell Movement/genetics; Cell Movement/immunology; Chemokine CXCL12/genetics; Chemokine CXCL12/immunology; Chemokine CXCL12/metabolism; Humans; Mice; Mice, Mutant Strains; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins/immunology; Proto-Oncogene Proteins/metabolism; Receptors, CXCR4/genetics; Receptors, CXCR4/immunology; Receptors, CXCR4/metabolism; Signal Transduction/genetics; Signal Transduction/immunology; T-Lymphocytes/immunology; T-Lymphocytes/metabolism; Up-Regulation/genetics; Up-Regulation/immunology; Wnt Proteins/genetics; Wnt Proteins/immunology; Wnt Proteins/metabolism; beta Catenin/genetics; beta Catenin/immunology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:WNT5A

involved_in

GO:0032722: positive regulation of chemokine production

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:WNT5A

involved_in

GO:0010820: positive regulation of T cell chemotaxis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:WNT5A

involved_in

GO:0045080: positive regulation of chemokine biosynthetic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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