TIM-3, a potential target for sepsis therapy.

Abstract

Immune dysregulation is one of the leading causes of mortality in patients with sepsis. T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), a negative costimulatory molecule, is pivotal for immune regulation during sepsis. The effects of TIM-3 appear to be bidirectional: in the early stages of sepsis, upregulation of TIM-3 may help attenuate inflammation, whereas its sustained overexpression in later stages and ligand binding promotes immune apoptosis or exhaustion, which suppresses immune responses. Furthermore, TIM-3 synergizes with other immune checkpoint molecules (e.g., programmed cell death receptor-1), exacerbates immunosuppression, and increases the risk of secondary infections. Blocking the TIM-3 signaling pathway can restore immune cell function and may be a novel therapeutic strategy for sepsis. Although TIM-3 holds promise as both a biomarker and a therapeutic target, its mechanisms are complex and may vary across disease stages, which necessitates further research to optimize targeted interventions. Future studies should focus on elucidating the dynamic signaling pathways of TIM-3, developing combination immunotherapies, and conducting clinical trials to validate its safety and efficacy in sepsis treatment.