The field of tissue-immune interactions has undergone significant transformation as emerging evidence demonstrates the centrality of local microenvironments in directing T cell biology. Historically, T cell differentiation and effector functions have been predominantly examined within lymphoid organs; however, recent studies reveal that tissues themselves are active participants, shaping T cell responses through dynamic communication with resident stromal and parenchymal cells. This evolving paradigm highlights a complex web of reciprocal signals—ranging from cytokines and chemokines to metabolic and epigenetic modifications—that govern the specialization, localization, and memory formation of T cells. Despite substantial advances, key questions remain regarding the precise molecular and cellular mechanisms mediating this crosstalk, the extent to which tissue-derived cues modulate immune balance, and how these processes influence disease tolerance, immune adaptation, and pathological inflammation.

Recent technological advances, such as single-cell and spatial omics, sophisticated imaging, and in vivo lineage tracing, have started to unravel the heterogeneity and dynamic behaviors of T cells in various tissue niches. Landmark studies now define tissue-resident memory T cells as critical sentinels of local immunity, while also uncovering pivotal roles for tissue-specific antigen presentation and metabolic adaptation in tuning T cell persistence and function. Yet, there remains a gap in our integrated understanding of how non-hematopoietic tissue elements, microenvironmental conditions, and systemic signals coordinate to sculpt T cell responses, especially under both homeostatic and disease states.

This Research Topic aims to elucidate the principles and mechanisms underlying tissue-immune crosstalk that instruct T cell fate decisions, specialization, and homeostasis. Through an emphasis on bidirectional communication between T cells and their tissue environment, we seek contributions that dissect fundamental regulatory circuits governing host defense, tolerance, and immune plasticity in health and pathology.

To gather further insights in tissue-specific regulation of T cell biology, we welcome articles addressing, but not limited to, the following themes:

-Tissue-specific antigen presentation and T cell activation
-Stromal and parenchymal cell–T cell interactions
-Microenvironmental influences on T cell metabolism and epigenetic programming
-Establishment, maintenance, and functions of tissue-resident memory T cells
-Impact of local cytokines, chemokines, and other soluble factors on T cell fate
-Spatial organization and migration of T cells within tissues
-Systems immunology and translational approaches for manipulating tissue-T cell crosstalk

The topic editors declare no conflict of interest

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Tissue‑immune crosstalk: Mechanisms and implications for T cell function and homeostasis

Tissue‑immune crosstalk: Mechanisms and implications for T cell function and homeostasis