Dynamic intravital imaging of cell-cell interactions in the lymph node.

In the last decade, the application of 2-photon intravital microscopy as a tool to study cell interactions in different areas of the immune system has offered an unprecedented opportunity to understand the complexity of cell behavior in relation to immune functions. In this review we describe the latest advances in the field of live imaging in the lymph nodes, grouping the different cell populations in 2 compartments according to their motility: the sessile compartment, which is formed by resident cells of stromal origin, macrophages, and resident dendritic cells, and the motile compartment, which is mainly formed by T and B lymphocytes. Here we review how the use of in vivo imaging has contributed to our understanding of the role of these cells in the initiation of the immune response in the draining lymph nodes.

Stealth mRNA nanovaccines to control lymph node trafficking.

mRNA-based vaccines symbolize a new paradigm shift in personalized medicine for the treatment of infectious and non-infectious diseases. However, the reactogenicity associated with the currently approved formulations limits their applicability in autoinflammatory disorders, such as tumour therapeutics. In this study, we present a delivery system showing controlled immunogenicity and minimal non-specific inflammation, allowing for selective delivery of mRNA to antigen presenting cells (APCs) within the medullary region of the lymph nodes. Our platform offers precise control over the trafficking of nanoparticles within the lymph nodes by optimizing stealth and targeting properties, as well as the subsequent opsonization process. By targeting specific cells, we observed a potent adaptive and humoral immune response, which holds promise for preventive and therapeutic anti-tumoral vaccines. Through spatial programming of nanoparticle distribution, we can promote robust immunization, thus improving and expanding the utilization of mRNA vaccines. This innovative approach signifies a remarkable step forward in the field of targeted nanomedicine.