The CLEC-2-podoplanin axis controls the contractility of fibroblastic reticular cells and lymph node microarchitecture

被引：210

作者：

Astarita, Jillian L. ^{[1
,2
]}

Cremasco, Viviana ^{[2
]}

Fu, Jianxin ^{[3
,4
]}

Darnell, Max C. ^{[5
,6
]}

Peck, James R. ^{[2
]}

Nieves-Bonilla, Janice M. ^{[2
]}

Song, Kai ^{[3
,4
]}

Kondo, Yuji ^{[3
,4
]}

Woodruff, Matthew C. ^{[1
,7
]}

Gogineni, Alvin ^{[8
]}

Onder, Lucas ^{[9
]}

Ludewig, Burkhard ^{[9
]}

Weimer, Robby M. ^{[8
]}

Carroll, Michael C. ^{[7
]}

Mooney, David J. ^{[5
,6
]}

Xia, Lijun ^{[3
,4
]}

Turley, Shannon J. ^{[2
,10
,11
]}

机构：

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

[2] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA

[3] Oklahoma Med Res Fdn, Cardiovasc Biol Res Program, Oklahoma City, OK 73104 USA

[4] Univ Oklahoma, Hlth Sci Ctr, Dept Biochem & Mol Biol, Oklahoma City, OK 73190 USA

[5] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA

[6] Harvard Univ, Wyss Inst Biol Inspired Engn, Cambridge, MA 02138 USA

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

[8] Genentech Inc, Dept Biomed Imaging, San Francisco, CA USA

[9] Kantonal Hosp, Inst Immunobiol, St Gallen, Switzerland

[10] Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA USA

[11] Genentech Inc, Dept Canc Immunol, San Francisco, CA USA

来源：

NATURE IMMUNOLOGY | 2015年 / 16卷 / 01期

基金：

美国国家卫生研究院; 美国国家科学基金会;

关键词：

EPITHELIAL-MESENCHYMAL TRANSITION; DENDRITIC CELLS; RECEPTOR CLEC-2; TUMOR INVASION; T-CELLS; PODOPLANIN; GROWTH; HOMEOSTASIS; IMMUNITY; T1-ALPHA/PODOPLANIN;

D O I：

10.1038/ni.3035

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

In lymph nodes, fibroblastic reticular cells (FRCs) form a collagen-based reticular network that supports migratory dendritic cells (DCs) and T cells and transports lymph. A hallmark of FRCs is their propensity to contract collagen, yet this function is poorly understood. Here we demonstrate that podoplanin (PDPN) regulates actomyosin contractility in FRCs. Under resting conditions, when FRCs are unlikely to encounter mature DCs expressing the PDPN receptor CLEC-2, PDPN endowed FRCs with contractile function and exerted tension within the reticulum. Upon inflammation, CLEC-2 on mature DCs potently attenuated PDPN-mediated contractility, which resulted in FRC relaxation and reduced tissue stiffness. Disrupting PDPN function altered the homeostasis and spacing of FRCs and T cells, which resulted in an expanded reticular network and enhanced immunity.

引用

页码：75 / +

页数：12

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