Gut-derived hyodeoxycholate reprograms the spleen-eye immunometabolic axis to suppress autoimmune uveitis - PubMed
7 hours ago
- #Bile acids
- #Immunometabolism
- #Autoimmune uveitis
- Autoimmune uveitis (AU) lacks targeted therapies beyond immunosuppression.
- Hyodeoxycholate (HDCA), a gut-derived secondary bile acid, was identified as a key immunometabolic regulator in AU.
- Metabolomics showed systemic depletion of HDCA and oleic acid (C18:1n9) in AU patients and experimental AU (EAU) mice, correlating with disease severity.
- HDCA administration attenuated EAU by reducing pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and elevating IL-10.
- HDCA inhibits Farnesoid X Receptor in splenic red pulp macrophages, activating SREBP1c-dependent fatty acid synthase, enhancing oleic acid production.
- Systemic oleic acid suppresses ocular Th17 responses and promotes M2 macrophage polarization, enhancing anti-inflammatory immunity.
- The findings define a spleen-to-eye immunometabolic axis driven by HDCA-mediated macrophage reprogramming, positioning HDCA as a promising therapeutic for AU.