TY - JOUR
T1 - Activation of Wnt5A signaling is required for CXC chemokine ligand 12-mediated T-cell migration
AU - Ghosh, Manik C.
AU - Collins, Gary D.
AU - Vandanmagsar, Bolormaa
AU - Patel, Kalpesh
AU - Brill, Margaret
AU - Carter, Arnell
AU - Lustig, Ana
AU - Becker, Kevin G.
AU - Wood, William W.
AU - Emeche, Chineye D.
AU - French, Amanda D.
AU - O'Connell, Michael P.
AU - Xu, Mai
AU - Weeraratna, Ashani T.
AU - Taub, Dennis D.
PY - 2009/11/19
Y1 - 2009/11/19
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2008-08-175869
DO - 10.1182/blood-2008-08-175869
M3 - Article
C2 - 19520808
AN - SCOPUS:70349310357
VL - 114
SP - 1366
EP - 1373
JO - Blood
JF - Blood
SN - 0006-4971
IS - 7
ER -