TY - JOUR
T1 - Activation of Toll-like Receptor-2 by Endogenous Matrix Metalloproteinase-2 Modulates Dendritic-Cell-Mediated Inflammatory Responses
AU - Godefroy, Emmanuelle
AU - Gallois, Anne
AU - Idoyaga, Juliana
AU - Merad, Miriam
AU - Tung, Navpreet
AU - Monu, Ngozi
AU - Saenger, Yvonne
AU - Fu, Yichun
AU - Ravindran, Rajesh
AU - Pulendran, Bali
AU - Jotereau, Francine
AU - Trombetta, Sergio
AU - Bhardwaj, Nina
N1 - Publisher Copyright:
© 2014 The Authors.
PY - 2014/12/11
Y1 - 2014/12/11
N2 - 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.
AB - 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.
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U2 - 10.1016/j.celrep.2014.10.067
DO - 10.1016/j.celrep.2014.10.067
M3 - Article
C2 - 25466255
AN - SCOPUS:84915766493
SN - 2211-1247
VL - 9
SP - 1856
EP - 1870
JO - Cell Reports
JF - Cell Reports
IS - 5
ER -