Objective:

To synthesize the molecular and immunometabolic mechanisms underlying Treg exhaustion in uveitis, emphasizing its critical role in disease pathology and evaluating therapeutic strategies.

Key Findings:

• Tregs are crucial for maintaining ocular homeostasis but exhibit quantitative reduction and functional exhaustion in uveitis, which complicates treatment.
• Distinct patterns of Treg dysfunction are observed in Behçet’s disease, VKH disease, and HLA-B27-associated uveitis, suggesting tailored treatment approaches.
• Treg exhaustion is linked to altered expression of surface molecules and metabolic dysregulation, which may serve as therapeutic targets.

Interpretation:

The findings highlight the complexity of Treg dysfunction in uveitis and suggest that personalized therapeutic approaches, tailored to specific disease subtypes, are necessary for effective management.

Limitations:

• Many mechanistic studies rely on experimental autoimmune uveitis models, which may not fully represent human disease heterogeneity, potentially limiting the applicability of findings.

Conclusion:

Restoring Treg function presents a promising therapeutic avenue for managing uveitis, with ongoing research needed to refine these strategies and enhance treatment efficacy.