Imaging techniques: new insights into chemokine/chemokine receptor biology at the immune system

Our current knowledge of molecular and cellular responses in vivo is based mainly on event reconstruction from time-freeze observations. Conventional biochemical and genetic methods consider the cell as an individual entity and ligand/receptor pairs as isolated systems. In addition, the data refer to the average behavior of a pool of cells and/or receptors removed from their real-life context. The use of new technologies, particularly real-time imaging approaches, is showing us that biological responses are highly dynamic and extremely dependent on the context in which they take place, and therefore much more diverse than initially envisaged. This review focuses on the mechanistic insights that new imaging techniques, such as those based on resonance energy transfer and two-photon microscopy, contribute to our understanding of how receptors work within a single cell, and how cells work within a tissue. Cell movement is a complex and regulated process; it has a key role in embryogenesis, organogenesis, wound-healing and tumor invasion. Nonetheless, it is in immune system homeostasis and response that cell movement becomes essential. For this reason, immunology is being radically transformed and enriched by these new approaches. We will discuss the use of these techniques for studying chemokine/chemokine receptors and their role in the immune system function, and comment on the potential contribution to the design of therapeutic strategies.