TY - JOUR
T1 - Podoplanin-Rich Stromal Networks Induce Dendritic Cell Motility via Activation of the C-type Lectin Receptor CLEC-2
AU - Acton, Sophie E.
AU - Astarita, Jillian L.
AU - Malhotra, Deepali
AU - Lukacs-Kornek, Veronika
AU - Franz, Bettina
AU - Hess, Paul R.
AU - Jakus, Zoltan
AU - Kuligowski, Michael
AU - Fletcher, Anne L.
AU - Elpek, Kutlu G
AU - Bellemare-Pelletier, Angelique
AU - Sceats, Lindsay
AU - Reynoso, Erika D
AU - Gonzalez, Santiago F
AU - Graham, Daniel B.
AU - Chang, Jonathan
AU - Peters, Anneli
AU - Woodruff, Matthew C.
AU - Kim, Young-A.
AU - Swat, Wojciech
AU - Morita, Takashi
AU - Kuchroo, Vijay
AU - Carroll, Michael C
AU - Kahn, Mark L
AU - Wucherpfennig, Kai W
AU - Turley, Shannon J
PY - 2012/8/24
Y1 - 2012/8/24
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84865401654&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2012.05.022
DO - 10.1016/j.immuni.2012.05.022
M3 - Article
C2 - 22884313
AN - SCOPUS:84865401654
SN - 1074-7613
VL - 37
SP - 276
EP - 289
JO - Immunity
JF - Immunity
IS - 2
ER -
