Curr Opin Immunol. 2026 Aug 27;102:102836. doi: 10.1016/j.coi.2026.102836. Online ahead of print.
ABSTRACT
Intestinal immunity is coordinated by the spatial organization and temporal regulation of immune cells within a complex, antigen-rich environment. In this review, we discuss the latest advances in our understanding of how these two fundamental dimensions together shape intestinal immune homeostasis. We first examine the temporal dynamics of intestinal immunity, ranging from prenatal immune development, early-life immune education, and differentiation established by maternal factors and dietary changes. We discuss recent discoveries identifying RORγt-expressing antigen-presenting cells as key regulators of oral tolerance, providing a mechanism for how transient developmental windows establish long-lasting immune homeostasis. We then explore the spatial organization of intestinal immune cells, from regional specialization along the length of the gastrointestinal tract to compartment-specific immune populations, as well as micro-niches revealed by emerging spatial technologies. We review specialized chemokine networks, cellular interactions, and the microenvironments that coordinate immune responses in distinct intestinal regions. As we face increasingly detailed spatiotemporal maps, the next challenge will be to translate all this information into mechanisms underpinning how immune niches are established and maintained to promote intestinal health.
PMID:42660009 | DOI:10.1016/j.coi.2026.102836