title: Activation of toll-like receptor-2 by endogenous matrix metalloproteinase-2 modulates dendritic-cell-mediated inflammatory responses.
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 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.
authors.affiliation: Mount Sinai School of Medicine, Tisch Cancer Institute, New York, NY 10029, USA.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Godefroy
authors.affiliation: Mount Sinai School of Medicine, Tisch Cancer Institute, New York, NY 10029, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Gallois
authors.affiliation: Mount Sinai School of Medicine, Tisch Cancer Institute, New York, NY 10029, USA; Laboratory of Cellular Physiology and Immunology and Chris Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York, NY 10065, USA; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Juliana
authors.initials: J
authors.lastname: Idoyaga
authors.affiliation: Mount Sinai School of Medicine, Tisch Cancer Institute, New York, NY 10029, USA.
authors.forename: Miriam
authors.initials: M
authors.lastname: Merad
authors.affiliation: Mount Sinai School of Medicine, Tisch Cancer Institute, New York, NY 10029, USA.
authors.forename: Navpreet
authors.initials: N
authors.lastname: Tung
authors.affiliation: New York University Langone Medical Center, Cancer Institute, New York, NY 10016, USA.
authors.forename: Ngozi
authors.initials: N
authors.lastname: Monu
authors.affiliation: Mount Sinai School of Medicine, Tisch Cancer Institute, New York, NY 10029, USA.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Saenger
authors.affiliation: Mount Sinai School of Medicine, Tisch Cancer Institute, New York, NY 10029, USA.
authors.forename: Yichun
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Emory Vaccine Center, Department of Pathology, Emory University, Atlanta, GA 30322, USA.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Ravindran
authors.affiliation: Emory Vaccine Center, Department of Pathology, Emory University, Atlanta, GA 30322, USA.
authors.forename: Bali
authors.initials: B
authors.lastname: Pulendran
authors.affiliation: INSERM U892, 44093 Nantes, France.
authors.forename: Francine
authors.initials: F
authors.lastname: Jotereau
authors.affiliation: New York University Langone Medical Center, Cancer Institute, New York, NY 10016, USA.
authors.forename: Sergio
authors.initials: S
authors.lastname: Trombetta
authors.affiliation: Mount Sinai School of Medicine, Tisch Cancer Institute, New York, NY 10029, USA. Electronic address: nina.bhardwaj@mssm.edu.
authors.forename: Nina
authors.initials: N
authors.lastname: Bhardwaj
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology*; D057809:HEK293 Cells; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D020778:Matrix Metalloproteinase 2 / Q000502:physiology*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D053278:OX40 Ligand / Q000378:metabolism; D011485:Protein Binding; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D053278:OX40 Ligand; C495342:TLR2 protein, human; C439524:TNF protein, human; C089251:TNFSF4 protein, human; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9