Immunometabolic regulation and tissue-resident immunity in autoimmune uveitis: from genetic susceptibility to the gut-spleen-eye axis.

OBJECTIVE AND

DESIGN

This narrative review synthesizes current evidence on the immunopathogenesis of autoimmune uveitis(AU), with particular emphasis on genetic susceptibility, immunometabolic dysregulation, tissue-resident immunity, and the proposed gut-spleen-eye immunometabolic axis.

MATERIAL AND SUBJECTS: Published genetic, clinical, experimental, and in vitro studies addressing immune-mediated uveitis and related mechanistic pathways were summarized.

TREATMENT: Not applicable.

METHODS

We summarized evidence on subtype-associated genetic factors, Th17-centered immunometabolic reprogramming, retinal microglial and myeloid responses, innate-adaptive immune interactions, and gut-derived metabolic regulation, with attention to evidence level and translational relevance.

RESULTS

Genetic susceptibility showed the clearest subtype specificity, including HLA-B27/ERAP1-associated acute anterior uveitis, IL23R-C1orf141-associated Vogt-Koyanagi-Harada disease, HLA-B51-ERAP1-associated Behçet disease, and NOD2-associated Blau syndrome. Experimental and clinical evidence further links Th17 dysregulation to AU, whereas most pathway-specific metabolic, microglial, macrophage, retinal vascular, and gut-derived mechanisms remain supported mainly by experimental autoimmune uveitis or in vitro studies. The proposed HDCA-red pulp macrophage-oleic acid pathway may integrate systemic metabolic and immune regulation, but its relevance to defined human AU subtypes remains uncertain.

CONCLUSIONS

AU is mechanistically heterogeneous, and current evidence supports phenotype-stratified validation of candidate pathways before translation into targeted therapeutic strategies.