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

被引：222

作者：

Acton, Sophie E. ^{[1
,2
]}

Astarita, Jillian L. ^{[1
,3
]}

Malhotra, Deepali ^{[1
,3
]}

Lukacs-Kornek, Veronika ^{[1
]}

Franz, Bettina ^{[1
]}

Hess, Paul R. ^{[4
,5
]}

Jakus, Zoltan ^{[4
,5
]}

Kuligowski, Michael ^{[6
,7
,8
]}

Fletcher, Anne L. ^{[1
]}

Elpek, Kutlu G. ^{[1
]}

Bellemare-Pelletier, Angelique ^{[1
]}

Sceats, Lindsay ^{[1
]}

Reynoso, Erika D. ^{[1
]}

Gonzalez, Santiago F. ^{[6
,7
,8
]}

Graham, Daniel B. ^{[9
]}

Chang, Jonathan ^{[1
,3
]}

Peters, Anneli ^{[10
]}

Woodruff, Matthew ^{[3
]}

Kim, Young-A. ^{[6
,7
,8
]}

Swat, Wojciech ^{[9
]}

Morita, Takashi ^{[11
]}

Kuchroo, Vijay ^{[10
]}

Carroll, Michael C. ^{[6
,7
,8
]}

Kahn, Mark L. ^{[4
,5
]}

Wucherpfennig, Kai W. ^{[1
]}

Turley, Shannon J. ^{[1
,12
]}

机构：

[1] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA

[2] UCL, Dept Cell & Dev Biol, London WC1E 6BT, England

[3] Harvard Univ, Sch Med, Div Med Sci, Boston, MA 02115 USA

[4] Univ Penn, Dept Med, Philadelphia, PA 19104 USA

[5] Univ Penn, Cardiovasc Inst, Philadelphia, PA 19104 USA

[6] Harvard Univ, Immune Dis Inst, Sch Med, Boston, MA 02115 USA

[7] Harvard Univ, Program Cellular & Mol Med, Sch Med, Childrens Hosp,Dept Pediat, Boston, MA 02115 USA

[8] Harvard Univ, Sch Med, Program Cellular & Mol Med, Childrens Hosp,Dept Pathol, Boston, MA 02115 USA

[9] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA

[10] Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA

[11] Meiji Pharmaceut Univ, Dept Biochem, Kiyose, Tokyo 2048588, Japan

[12] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA

来源：

IMMUNITY | 2012年 / 37卷 / 02期

基金：

美国国家科学基金会; 美国国家卫生研究院; 英国惠康基金; 英国医学研究理事会;

关键词：

SECONDARY LYMPHOID ORGANS; IN-VIVO; LYMPHATIC VESSELS; RHO; MIGRATION; RAC; NEUTROPHILS; INVASION; GTPASES; ROLES;

D O I：

10.1016/j.immuni.2012.05.022

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：276 / 289

页数：14

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