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

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

来源：Blood, 2009, 114(7): 1366-1373.

DOI：10.1182/blood-2008-08-175869

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. (Blood. 2009;114:1366-1373)

• 出版日期2009-8-13
• 单位NIH