Chemokines in Immunity
Mariagrazia Uguccioni, Group Leader
Our research interest remains focused on Chemokine activities in physiology and pathology, with an emphasis on the mechanisms governing fine-tuning modulation of their expression and activity. Chemokines are secreted proteins and have emerged as key controllers of integrin function and cell locomotion. The effects of chemokines are mediated by seven transmembrane domain receptors coupled to GTP-binding proteins, which are differentially expressed in a wide range of cell types. The resulting combinatorial diversity in responsiveness to chemokines guarantees the proper tissue distribution of distinct leukocyte subsets under normal and inflammatory/pathological conditions. A vast range of in situ experiments, aimed at understanding which chemokines are produced in specific circumstances, has revealed that a variety of chemokines can be concomitantly produced at target sites of leukocyte trafficking and homing. This renders the chemokine system a good target for therapy, and has increased the search by pharmaceutical companies for small molecule chemokine antagonists. While we understand the effects of different chemokines individually, much less is known about the potential consequences of the expression of multiple chemokines, cytokines, toll-like receptor ligands or other inflammatory molecules on leukocyte migration and function. Our group discovered the existence of additional features of chemokines: their ability to antagonize or enhance, as synergy-inducing chemokines, the activity of other chemokines.