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, Z. 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 Swat & 6 others Takashi Morita, Vijay Kuchroo, Michael C. Carroll, Mark L. Kahn, Kai W. Wucherpfennig, Shannon J. Turley

Research output: Contribution to journalArticle

149 Citations (Scopus)

Abstract

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
Pages (from-to)276-289
Number of pages14
JournalImmunity
Volume37
Issue number2
DOIs
Publication statusPublished - Aug 24 2012

Fingerprint

C-Type Lectins
Dendritic Cells
Cell Movement
Myosin Light Chains
Adaptive Immunity
Lymph
Actin Cytoskeleton
Actins
Blood Cells
Glycoproteins
Blood Platelets
Down-Regulation
Lymph Nodes
Phosphorylation
T-Lymphocytes
Membranes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

Acton, S. E., Astarita, J. L., Malhotra, D., Lukacs-Kornek, V., Franz, B., Hess, P. R., ... Turley, S. J. (2012). Podoplanin-Rich Stromal Networks Induce Dendritic Cell Motility via Activation of the C-type Lectin Receptor CLEC-2. Immunity, 37(2), 276-289. https://doi.org/10.1016/j.immuni.2012.05.022

Podoplanin-Rich Stromal Networks Induce Dendritic Cell Motility via Activation of the C-type Lectin Receptor CLEC-2. / Acton, Sophie E.; Astarita, Jillian L.; Malhotra, Deepali; Lukacs-Kornek, Veronika; Franz, Bettina; Hess, Paul R.; Jakus, Z.; Kuligowski, Michael; Fletcher, Anne L.; Elpek, Kutlu G.; Bellemare-Pelletier, Angelique; Sceats, Lindsay; Reynoso, Erika D.; Gonzalez, Santiago F.; Graham, Daniel B.; Chang, Jonathan; Peters, Anneli; Woodruff, Matthew; Kim, Young A.; Swat, Wojciech; Morita, Takashi; Kuchroo, Vijay; Carroll, Michael C.; Kahn, Mark L.; Wucherpfennig, Kai W.; Turley, Shannon J.

In: Immunity, Vol. 37, No. 2, 24.08.2012, p. 276-289.

Research output: Contribution to journalArticle

Acton, SE, Astarita, JL, Malhotra, D, Lukacs-Kornek, V, Franz, B, Hess, PR, Jakus, Z, Kuligowski, M, Fletcher, AL, Elpek, KG, Bellemare-Pelletier, A, Sceats, L, Reynoso, ED, Gonzalez, SF, Graham, DB, Chang, J, Peters, A, Woodruff, M, Kim, YA, Swat, W, Morita, T, Kuchroo, V, Carroll, MC, Kahn, ML, Wucherpfennig, KW & Turley, SJ 2012, 'Podoplanin-Rich Stromal Networks Induce Dendritic Cell Motility via Activation of the C-type Lectin Receptor CLEC-2', Immunity, vol. 37, no. 2, pp. 276-289. https://doi.org/10.1016/j.immuni.2012.05.022
Acton, Sophie E. ; Astarita, Jillian L. ; Malhotra, Deepali ; Lukacs-Kornek, Veronika ; Franz, Bettina ; Hess, Paul R. ; Jakus, Z. ; Kuligowski, Michael ; Fletcher, Anne L. ; Elpek, Kutlu G. ; Bellemare-Pelletier, Angelique ; Sceats, Lindsay ; Reynoso, Erika D. ; Gonzalez, Santiago F. ; Graham, Daniel B. ; Chang, Jonathan ; Peters, Anneli ; Woodruff, Matthew ; Kim, Young A. ; Swat, Wojciech ; Morita, Takashi ; Kuchroo, Vijay ; Carroll, Michael C. ; Kahn, Mark L. ; Wucherpfennig, Kai W. ; Turley, Shannon J. / Podoplanin-Rich Stromal Networks Induce Dendritic Cell Motility via Activation of the C-type Lectin Receptor CLEC-2. In: Immunity. 2012 ; Vol. 37, No. 2. pp. 276-289.
@article{5eb9eefcd631496088c2404286fc0119,
title = "Podoplanin-Rich Stromal Networks Induce Dendritic Cell Motility via Activation of the C-type Lectin Receptor CLEC-2",
abstract = "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.",
author = "Acton, {Sophie E.} and Astarita, {Jillian L.} and Deepali Malhotra and Veronika Lukacs-Kornek and Bettina Franz and Hess, {Paul R.} and Z. Jakus and Michael Kuligowski and Fletcher, {Anne L.} and Elpek, {Kutlu G.} and Angelique Bellemare-Pelletier and Lindsay Sceats and Reynoso, {Erika D.} and Gonzalez, {Santiago F.} and Graham, {Daniel B.} and Jonathan Chang and Anneli Peters and Matthew Woodruff and Kim, {Young A.} and Wojciech Swat and Takashi Morita and Vijay Kuchroo and Carroll, {Michael C.} and Kahn, {Mark L.} and Wucherpfennig, {Kai W.} and Turley, {Shannon J.}",
year = "2012",
month = "8",
day = "24",
doi = "10.1016/j.immuni.2012.05.022",
language = "English",
volume = "37",
pages = "276--289",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "2",

}

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, Z.

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

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

UR - http://www.scopus.com/inward/citedby.url?scp=84865401654&partnerID=8YFLogxK

U2 - 10.1016/j.immuni.2012.05.022

DO - 10.1016/j.immuni.2012.05.022

M3 - Article

VL - 37

SP - 276

EP - 289

JO - Immunity

JF - Immunity

SN - 1074-7613

IS - 2

ER -