Immunometabolic and Spatiotemporal Control of Tissue‐Resident Memory T Cell Biology

ABSTRACT Tissue‐resident memory T (T RM ) cells populate most tissues, where they serve as sentinels to mediate local immune protection and tissue homeostasis. Distinct tissue microenvironments exhibit remarkable diversity in cellular composition, cytokines, chemokines, and nutrient availability. The ability of T RM cells to integrate these dynamic immune and metabolic cues is essential for their differentiation, persistence, and protective function. Recent advances have highlighted both shared and tissue‐specific mechanisms that direct T RM formation and heterogeneity. Here, we discuss the spatiotemporal and tissue‐specific regulation of T RM development in response to infection, focusing on immune and nutrient signals, transcriptional networks, and metabolic programs and signaling pathways that shape their fate. A better understanding of T RM heterogeneity and tissue‐specific programming will provide opportunities to advance immunotherapies that improve human health.