Authors:
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
Summary:
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.
Source:
Cell Reports; Vol. 9, Issue 5, 1856-1870 (12/11/14)