کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2042153 | 1073187 | 2014 | 15 صفحه PDF | دانلود رایگان |
• MMP-2 is shown to be a ligand for the Toll-like receptor 2
• MMP-2-dependent TLR2 triggering induces type 2 polarization via OX40L upregulation
• MMP-2 triggers TLR2 independently of its usual coreceptors, i.e., TLR1, 6, and 4
• MMP-2 polarizes TH2 immune responses in vivo in a TLR2-dependent manner
SummaryMatrix 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.
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Journal: - Volume 9, Issue 5, 11 December 2014, Pages 1856–1870