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

Emmanuelle Godefroy, Anne Gallois, Juliana Idoyaga, Miriam Merad, Navpreet Tung, Ngozi Monu, Yvonne Saenger, Yichun Fu, Rajesh Ravindran, Bali Pulendran, Francine Jotereau, Sergio Trombetta, Nina Bhardwaj

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

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-κB activation, OX40L upregulation on DCs, and ensuing TH2 differentiation. Significantly, MMP-2 polarizes Tcells toward type 2 responses invivo, 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. Godefroy etal. now demonstrate that matrix metalloproteinase-2 (MMP-2) directly interacts with and activates dendritic cells (DCs) via Toll-like receptor-2. MMP-2-exposed DCs upregulate OX40L, promoting type 2 polarization both invitro and invivo. This may represent a key immune regulatory mechanism involved in a variety of inflammatory disorders.

Original languageEnglish
Pages (from-to)1856-1870
Number of pages15
JournalCell Reports
Volume9
Issue number5
DOIs
StatePublished - 11 Dec 2014

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