Cell-intrinsic control of tissue-resident memory T cell fate and function

Tissue-resident memory T (TRM) cells are a key subset of adaptive immune memory, distinguished by their prolonged persistence in non-lymphoid sites such as the lung, skin, and gastrointestinal tract. Beyond their location, TRM cells exhibit a spectrum of durable functional states—ranging in cytotoxicity, cytokine production, proliferative potential, and exhaustion-like features—which define their capacity for local recall responses. While canonical markers such as CD69 and CD103 have been foundational for TRM identification, recent advances in single-cell and multi-omics technologies have uncovered a remarkable heterogeneity and nuance within the TRM compartment. Functional perturbation and fate-mapping studies now allow mapping of differentiation pathways and a direct link between molecular programs and immune protection or pathology. Fully unraveling how TRM identity is molecularly encoded and preserved will empower more predictive and targeted immune interventions.This Research Topic is dedicated to exploring the cell-intrinsic mechanisms governing TRM differentiation, maintenance, and functional versatility. Priorities include dissecting transcriptional networks, epigenetic memory, and post-transcriptional mechanisms that lock in or remodel TRM fate—especially in response to chronic antigen exposure, inflammation, or tumor development. Another focus is on the metabolic and organelle-level adaptations supporting TRM longevity and their rapid recall responses. We particularly encourage submissions that move beyond observational studies to causality-testing approaches—using genetic perturbations, lineage tracing, quantitative modeling, or systems immunology—so as to clarify mechanisms that determine TRM quality and durability. Ultimately, we seek insight into how these intrinsic programs can be harnessed to boost beneficial TRM responses or restrain their pathogenicity in chronic disease.We invite Original Research, Review, Mini Review, and Perspective articles that advance mechanistic and translational understanding of TRM cells. Areas of interest include, but are not limited to:o Transcriptional, epigenetic, and post-transcriptional regulation of TRM fate and longevityo Heterogeneity and plasticity of TRM cells, including activation, quiescence, and exhaustiono Clonal dynamics, memory imprinting, and antigen experience shaping TRM responseso Metabolic and organelle programs underlying TRM persistence and recall capacityo Strategies for engineering or modulating TRM programs in vaccination, immunotherapy, and limiting pathological TRM activity Topic editors: Jinyi Tang, Tianyang Mao, Harish Narasimhan Source: https://www.frontiersin.org/research-topics/82746/cell-intrinsic-control-of-tissue-resident-memory-t-cell-fate-and-function