Podoplanin-Rich Stromal Networks Induce Dendritic Cell Motility via Activation of the C-type Lectin Receptor CLEC-2

Sophie E. Acton, Jillian L. Astarita, Deepali Malhotra, Veronika Lukacs-Kornek, Bettina Franz, Paul R. Hess, Zoltan Jakus, Michael Kuligowski, Anne L. Fletcher, Kutlu G. Elpek, Angelique Bellemare-Pelletier, Lindsay Sceats, Erika D. Reynoso, Santiago F. Gonzalez, Daniel B. Graham, Jonathan Chang, Anneli Peters, Matthew Woodruff, Young A. Kim, Wojciech SwatTakashi Morita, Vijay Kuchroo, Michael C. Carroll, Mark L. Kahn, Kai W. Wucherpfennig, Shannon J. Turley

Research output: Contribution to journalArticlepeer-review

165 Scopus citations


To initiate adaptive immunity, dendritic cells (DCs) move from parenchymal tissues to lymphoid organs by migrating along stromal scaffolds that display the glycoprotein podoplanin (PDPN). PDPN is expressed by lymphatic endothelial and fibroblastic reticular cells and promotes blood-lymph separation during development by activating the C-type lectin receptor, CLEC-2, on platelets. Here, we describe a role for CLEC-2 in the morphodynamic behavior and motility of DCs. CLEC-2 deficiency in DCs impaired their entry into lymphatics and trafficking to and within lymph nodes, thereby reducing T cell priming. CLEC-2 engagement of PDPN was necessary for DCs to spread and migrate along stromal surfaces and sufficient to induce membrane protrusions. CLEC-2 activation triggered cell spreading via downregulation of RhoA activity and myosin light-chain phosphorylation and triggered F-actin-rich protrusions via Vav signaling and Rac1 activation. Thus, activation of CLEC-2 by PDPN rearranges the actin cytoskeleton in DCs to promote efficient motility along stromal surfaces.

Original languageEnglish (US)
Pages (from-to)276-289
Number of pages14
Issue number2
StatePublished - Aug 24 2012

Bibliographical note

Funding Information:
The authors are grateful to J. Campbell and B. Vander Lugt for CCR7 knockout mice; to L.-H. Ang, Y. Zheng, and S. Hagen for assistance with microscopy; and to R. Gelman for assistance with statistical analysis. They are also grateful to E. Sahai for critical reading of the manuscript. This work was supported by National Institutes of Health grants R01 DK074500 and P01 AI045757 (to S.J.T.), R01AI073718 and AI061077 (W.S.), and LLS (W.S., D.B.G.); a Wellcome Trust Henry Wellcome Postdoctoral Fellowship (to S.E.A.); a National Science Foundation Graduate Research Fellowship (to J.L.A.); a Benacerraf Postdoctoral Fellowship (to V.L.K.); a National Health Medical Research Council Postdoctoral Biomedical Training Fellowship (to A.L.F.); and a Seventh Framework Programme of the European Union (Marie Curie International Outgoing Fellowship 220044, to S.F.G.).

Fingerprint Dive into the research topics of 'Podoplanin-Rich Stromal Networks Induce Dendritic Cell Motility via Activation of the C-type Lectin Receptor CLEC-2'. Together they form a unique fingerprint.

Cite this