Processed single-cell RNA-seq data from: Regionalized immune programs define Peyer’s patches along the small intestine

Source paper abstract: The gut is the body’s largest portal to the external world, where immune tolerance to commensals and food antigens must coexist with protection against infections. This balance is achieved through barrier structures and site-specific immune programs within the intestinal parenchyma. Peyer’s patches (PPs) are key lymphoid organs embedded along the three main segments of the small intestine, where they regulate intestinal immunity. Yet, whether they are regionally specialized has remained unclear. Here we mapped the immune landscapes of duodenal, jejunal, and ileal PPs and uncover a multilayered regional specialization encoded across cellular composition, transcriptional state, niche architecture and immune function. While duodenal PPs preferentially support myeloid-rich environments and cytotoxic T-cell priming, jejunal and ileal PPs are biased toward humoral immunity. Mechanistically, commensal microbes and dietary antigens orchestrate this anatomic architecture in a region- and subset-specific manner. Physiologically, the proximal enrichment of cytotoxic programs is required to maintain segment-dependent control of bacterial burden. Finally, exposure to high-fat diets disrupted this organization, partially through diet-induced dysbiosis. These findings establish that PPs are functionally heterogeneous and harbor distinct, environmentally tuned immune programs along the intestine, providing a framework for understanding mucosal immunity and informing strategies to treat intestinal inflammation or design site-directed vaccines.