Spatial dynamics of human secondary lymphoid tissues 4281

Abstract Description Functional output of the immune system depends on spatial organization and cell coordination in secondary lymphoid tissues (SLT), but this organization is often unobservable with current technologies for high-resolution profiling of cell states and interactions. By applying multimodal spatial analyses to human SLT from healthy aging adults both at rest and during inflammatory responses, we aim to characterize the immune-structural cell organization that maintains SLT homeostasis at steady state and dictates local immune responses during activation. We have built a spatial transcriptomics computational analysis framework to detect cell composition, gene expression, and interaction gradients with respect to key anatomical structures in SLT. Application of this framework to tonsils and lymph nodes recapitulated expected follicular organization, chemokine gradients, and follicle polarization with respect to epithelium or lymphatic vasculature. We identified follicles in a range of early activation states, even in lymph nodes from individuals with no known infection, providing an opportunity to characterize the initial drivers of follicle activation. Lymph nodes from different body sites but not from differently aged donors demonstrated differences in immune responsiveness. We are investigating the cellular and molecular mechanisms of these differences to better understand the spatial dynamics that mediate effective immunity at the sites of interaction. Funding Sources This work was supported by the Allen Institute. Topic Categories Computational and Systems Immunology (COMP)