Activation of Wnt5A signaling is required for CXC chemokine ligand 12-mediated T-cell migration

Manik C. Ghosh, Gary D. Collins, Bolormaa Vandanmagsar, Kalpesh Patel, Margaret Brill, Arnell Carter, Ana Lustig, Kevin G. Becker, William W. Wood, Chineye D. Emeche, Amanda D. French, Michael P. O'Connell, Mai Xu, Ashani T. Weeraratna, Dennis D. Taub

Research output: Contribution to journalArticle

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 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.

Original languageEnglish (US)
Pages (from-to)1366-1373
Number of pages8
JournalBlood
Volume114
Issue number7
DOIs
StatePublished - Nov 19 2009

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Ghosh, M. C., Collins, G. D., Vandanmagsar, B., Patel, K., Brill, M., Carter, A., Lustig, A., Becker, K. G., Wood, W. W., Emeche, C. D., French, A. D., O'Connell, M. P., Xu, M., Weeraratna, A. T., & Taub, D. D. (2009). Activation of Wnt5A signaling is required for CXC chemokine ligand 12-mediated T-cell migration. Blood, 114(7), 1366-1373. https://doi.org/10.1182/blood-2008-08-175869