Intercellular Communication in the Inflammatory Response
Intercellular communication is fundamental to the innate and adaptive immune responses.
Our group is interested in the molecular basis of key communication processes involving immune cells, such as the formation of the immune synapse between antigen presenting cells (APC) and T cells and the migration of leukocytes across the endothelium. The immune synapse (IS) is a highly segregated structure formed at the contact site between the T cell and APC by the polarized reorganization of transmembrane and membraneassociated molecules. We are currently investigating the possibility that this structure permits the directional transfer of miRNA-loaded exosomes from T cell to APC, providing a specific means of cell-cell communication with important functional consequences for APC biology.
The interaction of leukocytes with the vascular endothelium is a highly regulated step-wise process that allows the selective recruitment of inflammatory leukocyte subsets to inflammatory foci, where they exert their effector functions. Understanding the supra-molecular organization of the receptors involved in this process is another of our main goals, with the ultimate aim of identifying new molecular targets for therapy. A related area of interest is the crucial roles played in inflammation by specific receptors: CD69, galectins, PSGL-1 and the tetraspanins CD9 and CD81. The biology of these molecules is being investigated using genedeficient mouse strains in models of diverse inflammatory diseases, including allergic asthma, experimental autoimmune myocarditis, delayed-contact hypersensitivity and DSS-induced ulcerative colitis.
We are also interested in T lymphocyte synthesis of nitric oxide (NO) and other soluble mediators that regulate the production of pro-inflammatory cytokines. Our interest here centers on the molecular mechanisms regulating polarized secretion during antigen-dependent T cell-APC interactions and the regulatory role of T-cell derived NO in vascular lesions.