Using evasins as tools to regulate the activation and recruitment of leukocytes to injury sites

Uncontrolled inflammation is a major public health issue. It is difficult to treat clinically and is not restricted to the devastating pneumonia resulting from covid-19 infections. Thus, there is an urgent need for anti-inflammatory therapies that apply to covid-19 but also to the many inflammatory disorders affecting humans. During evolution, ticks had to circumvent an attack by the immune system of their mammalian host. As such, ticks developed mechanisms that reduce inflammation while they feed on their host. One family of proteins that belongs to this anti-inflammatory system are the evasins. Evasins bind to chemokines, proteins that are crucial to attract leukocytes to the site of inflammation. There is, however, limited knowledge on the mechanisms evasins use to reduce the effects of chemokines in vivo. Do they only block interactions of chemokines with their G protein-coupled receptors? Do they affect chemokine presentation on glycosaminoglycans? Do they also influence the activity of chemokines by interfering with chemokine processing? Evasins and chemokines will be produced by chemical peptide synthesis. The potential interference of the evasins with the inflammatory activity of chemokines and its influence on the regulation of posttranslational chemokine processing will be investigated. Site-specific fluorescent labelling of evasins and chemokines will allow to investigate mechanisms of action in acute injury models by intravital microscopy. Moreover, the therapeutic potential of evasins to treat acute liver injury will be evaluated.