TLRs are a family of type I membrane proteins that play a fundamental role in sensing invasions and initiating immune response. When activated, TLRs form homo- or hetero-dimers that result in secretion of pro-inflammatory mediators. Uncontrolled activation of TLRs might lead to a number of pathologies ranging from cystic fibrosis, sepsis, Crohn’s disease and cancer.
We study the contribution of the transmembrane domains (TMDs) of TLRs to the receptors activation in different diseases. We designed a novel family of peptides that target the TMD of TLRs and successfully ameliorate sepsis and inflammatory bowel disease in in-vivo mice models. The underlying mechanism of peptide’s action is studies using various state of the art biochemical and biophysical methods.