2. Academic Validation
  3. Oleic acid regulates CD4+ T cells differentiation by targeting ODC1-mediated STAT5A phosphorylation in Vogt-Koyanagi-Harada disease

Oleic acid regulates CD4+ T cells differentiation by targeting ODC1-mediated STAT5A phosphorylation in Vogt-Koyanagi-Harada disease

  • Phytomedicine. 2025 Jun:141:156660. doi: 10.1016/j.phymed.2025.156660.
Weiting Liao 1,  Ruixue Hu 1,  Yan Ji 1,  Zhenyu Zhong 1,  Xinyue Huang 2,  Tao Cai 3,  Chunjiang Zhou 1,  Yao Wang 1,  Zi Ye 4,  Peizeng Yang 5
Affiliations

Affiliations

  • 1 Ophthalmology Medical Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory for the Prevention and Treatment of Major Blinding Eye Diseases, Chongqing Branch (Municipality Division) of National Clinical Research Centre for Ocular Diseases, Chongqing, China.
  • 2 Southwest Hospital/Southwest Eye Hospital, Third Military Medical University (Army Medical University), Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Jinfeng Laboratory, Chongqing, China.
  • 3 The First Affiliated Hospital of Chongqing Medical University, department of Dermatology, Chongqing, China.
  • 4 Ophthalmology Medical Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory for the Prevention and Treatment of Major Blinding Eye Diseases, Chongqing Branch (Municipality Division) of National Clinical Research Centre for Ocular Diseases, Chongqing, China. Electronic address: [email protected].
  • 5 Ophthalmology Medical Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory for the Prevention and Treatment of Major Blinding Eye Diseases, Chongqing Branch (Municipality Division) of National Clinical Research Centre for Ocular Diseases, Chongqing, China. Electronic address: [email protected].
PMID: 40203473 DOI: 10.1016/j.phymed.2025.156660
Abstract

Background: Vogt-Koyanagi-Harada (VKH) is a multisystemic autoimmune disorder characterized by bilateral panuveitis frequently accompanied by neurologic manifestations. While metabolic dysregulation is increasingly recognized in the context of autoimmune diseases, the role of specific metabolites in VKH disease remains unexplored.

Methods: Non-targeted and targeted metabolomics analysis, phospho-antibody array, proteome microarray, surface plasmon resonance, and molecular simulation were used to identify molecular target of OA.

Results: We investigated metabolic profile of VKH disease and found that oleic acid (OA) was enriched in this disease. A series of functional assays showed that OA could exacerbate experimental autoimmune uveitis (EAU) in association with increased frequency of Th1 and Th17 cells and decreased proportion of Treg cells in vitro. However, the specific molecular target of OA remains elusive. Through proteome microarrays, molecular simulations and surface plasmon resonance assays, Ornithine decarboxylase 1 (ODC1) was identified as target protein of OA. OA could bind to ODC1, increase ODC1 protein expression in both a time- and concentration-dependent manner and promote subsequently putrescine production. Phospho-antibody array analysis revealed that OA inhibited phosphorylation of STAT5A (Y694) in CD4+T cells, leading to imbalance of Th1/Th17 and Treg cells and decreased transcription of IL-10. OA upregulated ODC1 protein and putrescine levels through binding to LYS-78, inhibited phosphorylation of STAT5A protein and subsequently decreased binding of STAT5A at IL-10 promoter.

Conclusion: These results reveals that OA could be a crucial metabolite for modulation of CD4+T cell differentiation and that ODC1-mediated phosphorylation and transcriptional activity of STAT5A contributes to development of VKH disease progression, highlighting ODC1 as a novel therapeutic target in VKH disease.

Keywords

CD4+ T cells; Oleic acid (OA); Ornithine decarboxylase (ODC); Phosphorylation; Vogt-Koyanagi-Harada disease.

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