Activation of Toll-like Receptor-2 by Endogenous Matrix Metalloproteinase-2 Modulates Dendritic-Cell-Mediated Inflammatory Responses

被引：34

作者：

Godefroy, Emmanuelle ^{[1
]}

Gallois, Anne ^{[1
]}

Idoyaga, Juliana ^{[1
,2
,3
,4
]}

Merad, Miriam ^{[1
]}

Tung, Navpreet ^{[1
]}

Monu, Ngozi ^{[5
]}

Saenger, Yvonne ^{[1
]}

Fu, Yichun ^{[1
]}

Ravindran, Rajesh ^{[6
]}

Pulendran, Bali ^{[6
]}

Jotereau, Francine ^{[7
]}

Trombetta, Sergio ^{[5
]}

Bhardwaj, Nina ^{[1
]}

机构：

[1] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY 10029 USA

[2] Rockefeller Univ, Lab Cellular Physiol & Immunol, New York, NY 10065 USA

[3] Rockefeller Univ, Chris Browne Ctr Immunol & Immune Dis, New York, NY 10065 USA

[4] Stanford Univ, Sch Med, Dept Microbiol & Immunol, Stanford, CA 94305 USA

[5] NYU, Langone Med Ctr, Inst Canc, New York, NY 10016 USA

[6] Emory Univ, Dept Pathol, Emory Vaccine Ctr, Atlanta, GA 30322 USA

[7] INSERM, U892, F-44093 Nantes, France

来源：

CELL REPORTS | 2014年 / 9卷 / 05期

关键词：

ALLERGIC INFLAMMATION; PROTEIN-KINASE; T-CELLS; EXPRESSION; CANCER; INDUCTION; TLR2; TRANSCRIPTION; LIPOPEPTIDES; ANGIOGENESIS;

D O I：

10.1016/j.celrep.2014.10.067

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Matrix metalloproteinase-2 (MMP-2) is involved in several physiological mechanisms, including wound healing and tumor progression. We show that MMP-2 directly stimulates dendritic cells (DCs) to both upregulate OX40L on the cell surface and secrete inflammatory cytokines. The mechanism underlying DC activation includes physical association with Toll-like receptor-2 (TLR2), leading to NF-kappa B activation, OX40L upregulation on DCs, and ensuing TH2 differentiation. Significantly, MMP-2 polarizes T cells toward type 2 responses in vivo, in a TLR2-dependent manner. MMP-2-dependent type 2 polarization may represent a key immune regulatory mechanism for protection against a broad array of disorders, such as inflammatory, infectious, and autoimmune diseases, which can be hijacked by tumors to evade immunity.

引用

页码：1856 / 1870

页数：15

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