Intestinal T-cell migration: unraveling mechanisms and therapeutic implications.

Background

Intestinal T-cell migration links mucosal immunity with systemic immune homeostasis and contributes to immune surveillance, barrier defense, and peripheral tissue inflammation. Advances in single-cell omics, spatial analysis, and intravital imaging are reshaping our understanding of its subset specificity and tissue selectivity.

Aim

OF REVIEW This review summarizes the molecular mechanisms, microenvironmental regulation, pathological significance along the gut-organ axes, and related therapeutic strategies of intestinal T-cell migration, with a particular focus on how migratory imbalance contributes to intestinal and extraintestinal immune-mediated diseases. KEY SCIENTIFIC CONCEPTS REVIEWED Intestinal T-cell migration is jointly driven by gut imprinting, S1P-S1PR-mediated egress, chemokine-guided trafficking, integrin-dependent adhesion, and cytoskeletal remodeling, and is further regulated by metabolic, epigenetic, and microbial signals. This process is highly dependent on T-cell subset and tissue context: it promotes effector T-cell recruitment and inflammatory amplification in inflammatory bowel disease, manifests as restricted antitumor T-cell infiltration in colorectal cancer, and may contribute to distant tissue injury through the gut-organ axes. Existing S1PR modulators, integrin antagonists, and chemokine-targeted strategies have demonstrated the therapeutic tractability of migratory pathways; however, pathway redundancy, tissue heterogeneity, and impairment of protective immunity continue to limit their application. Future strategies should move beyond broad suppression of migration toward subset-, tissue-, and disease stage-specific precision modulation, combined with microbiota-based interventions and biomarker-guided stratification to improve therapeutic efficacy.