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.