UM File # 4366

Background
The Toll family of polypeptides is remarkably conserved across the taxonomic kingdoms, suggesting essential role in physiology. These peptides share homologous domains and signaling pathways, which are used to trigger inflammatory and immunological responses. However, the function of these proteins extends beyond host defense. As expressed on leukocytes, endothelial cells, and various parenchymal cells, Toll-like receptor 4 (TLR4) detects the products of microorganisms, which initiates signals leading to activation of NFKB, among other signaling that induce the expression of genes that incite inflammation and adaptive immunity. These responses sequester and clear microorganisms and heighten resistance of the host upon re-infection.

Technology Description
Researchers at the University of Michigan and another institution have developed methods and materials to modulate TLR activity in cells. In particular, CXCR4 binding agents may be administered to modulate the ability of TLRs to respond to agonists. These CXCR4 binding agents include anti-CXCR4 antibody and SDF-1 polypeptide to increase or decrease, respectively, TLR4 polypeptide activity in response to TLR agonist such as lipopolysaccahide, heparan sulfate, and viral nucleic acids.

Applications
• Modulation of TLR4 activity

Advantages
• Activity of TLR4 may be increased or decreased via use of different materials provided herein

File Number: 4366