Chemokines: Structure/Function Studies
Research area: Chemokines in Immunity
Group leaders: Mariagrazia Uguccioni
Status: In progress
Chemokines have emerged as key controllers of integrin function and cell locomotion. A vast range of in situ experiments has revealed that a variety of chemokines can be concomitantly produced in physiology, as well as in tumours. This renders the chemokine system a good target for therapy, and has increased the search, by pharmaceutical companies, for chemokine antagonists. While we understand well the effects of different chemokines one by one, much less was known about the potential consequences of the expression of multiple chemokines, cytokines, toll like receptor ligands or different inflammatory molecules, on cell responses to chemokines. Chemokine structure/function studies led us to identify chemokines that can act as natural antagonists by preventing natural agonist binding and the subsequent activation of the receptor. Recently, we have described chemokines that can act in synergism with chemokine receptor agonists, forming heterocomplexes able to induce functional responses at lower agonist concentration. There is no more doubt that the synergism between chemokines is crucial at the very early stage of inflammation, while the study of the role of molecules, such as the alarmin High Mobility Group Box 1 (HMGB1), that can synergise with chemokines is at its infancy.