Premium
CXCL12 mediates T‐cell migration via activation of the non‐canonical Wnt signaling pathway
Author(s) -
Ghosh Manik C.,
Collins Gary D,
Carter Arnell,
Vandanmagsar Bolormaa,
Brill Margaret,
Lustig Ana,
Becker Kevin G,
Wood William W,
Emeche Chineya D,
French Amanda D,
O'Connell Michael P,
Dissanayake Samudra K,
Weeraratne Ashani T,
Taub Dennis D
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1070.16
Subject(s) - wnt signaling pathway , microbiology and biotechnology , chemotaxis , signal transduction , chemokine , gene knockdown , chemistry , chemokine receptor , lrp5 , receptor , biology , gene , biochemistry
CXCL12 acts as a strong chemoattractant during inflammation and mediates its effects by binding and signaling through its receptor, CXCR4 to regulate the trafficking of cells. To better understand the pathways by which CXCL12 mediates T‐lymphocyte migration, we performed microarray analysis on resting and migrating T‐cells exposed to CXCL12. Through these analyses, we identified a number of unique signaling molecules induced by CXCL12 treatment including the induction of several members of the non‐canonical Wnt pathway. The mRNA and protein expression of Wnt5A along with its receptors Fzd2 and Fzd3 were significantly induced upon CXCL12 treatment in a biphasic and time‐dependent manner. In addition, the transcriptional activation of the Wnt5A promoter by CXCL12 was further confirmed by electrophoretic mobility shift assay (EMSA). siRNA and shRNA knockdown of Wnt5a in primary T cells and transformed T cell lines, respectively, significantly inhibited CXCR4 signaling and function suggesting an important role for the Wnt‐Fzd pathways in chemokine‐chemokine receptor function. Moreover, chemokine‐induced Wnt and Fzd molecules appear to play a critical role in PKC and Rac activation, MMP expression and actin polymerization in response to CXCL12 stimulation. Together, these results implicate the possible involvement of the non‐canonical Wnt signaling pathway in chemokine activation and T cell trafficking