Won't you be my neighbor? Control of the immune response by stromal and immune cell microenvironments within the...

Efficacious immune responses require the coordinated encounter of rare antigen-specific adaptive lymphocytes with their cognate innate antigen-presenting cells (APCs) in space and time. This spatiotemporal problem of immunity is solved by secondary lymphoid organs, such as lymph nodes (LNs), which coordinate adaptive immune responses by recruiting APCs and lymphocytes into close juxtaposition with tissue antigens drained from the periphery. A central tenet to the overall function of the LN is the spatial organization of leukocytes into discrete microenvironments orchestrated by the mesenchymal and endothelial cells, collectively termed LN stromal cells (LNSCs). The stromal-immune cell circuits are now appreciated to be critically important for the homeostatic, inflammatory, and resolution phases of LN responses. Akin to the structural units of the LN, we briefly summarize early observations that helped to characterize the complex niches now appreciated in murine and human LNs. We next delve into recent advancements in spatial multiomic technologies that yielded unrivaled insight into the complexity of LN niches and the intrinsic signals provided by LNSCs that govern immune responses.