Leukocyte movement is mostly driven by chemokines and their receptors, that belong to the G protein coupled receptors (GPCRs). This pair regulate a myriad of physio-pathological processes, ranging from cellular and humoral immune response to lymphocyte recruitment during chronic inflammation and tumor metastasis.

My work has focused on the study of chemokine receptor conformations at the cell membrane and their functional relevance. Chemokine receptors are highly dynamic and are modulated by coexpression of other chemokine receptors, interaction with other GPCRs or with transmembrane proteins, and by the concentration of their ligands. Ultimately, their membrane organization depends on the cell type and the milieu.

Currently, the main goal of my research is to gain a deeper understanding of the chemokine receptor biology during T cell migration. These receptors are organized at the cell membrane as monomers, dimers and small oligomers (nanoclusters, 3 receptors) in resting cells. Upon chemokine stimulation, both the size and the percentage of these oligomers (nanoclusters) increase at the cell membrane. We have recently found that there is a correlation between the size of these nanoclusters and the cell migration capacity. However, the organization of these receptors during leukocyte migration and the underlying molecular mechanisms are still unknown.

We set up assays to study the chemokine receptor stoichiometry and dynamic during T cell movement, both prior lymphocyte extravasation and during interstitial migration. Furthermore, we are interested in identifying possible target proteins that regulate the chemokine receptor-spatiotemporal organization.

This knowledge will help discovering new therapeutic targets to achieve a thorough modulation of T cell adhesion and migration capacity in pathologies involving chronic inflammation, mass leukocyte infiltration or tumor cell dissemination.

Funding: