2. Academic Validation
  3. Irisin Alleviates Autoimmune Uveitis Through Promoting Retinal Microglial M1 to M2 Phenotypic Polarization Mediated by HIF-1α Pathway

Irisin Alleviates Autoimmune Uveitis Through Promoting Retinal Microglial M1 to M2 Phenotypic Polarization Mediated by HIF-1α Pathway

  • Inflammation. 2024 Sep 29. doi: 10.1007/s10753-024-02149-5.
Meiqi Wang # 1,  Xue Huang # 1,  Jia Shu # 2,  Hongxi Li 3,  Tao Yang 1,  Na Li 1,  Peizeng Yang 4
Affiliations

Affiliations

  • 1 Department of Ophthalmology, Joint Research Laboratory for Ocular Immunology and Retinal Injury Repair, The First Affiliated Hospital of Zhengzhou University, Henan International, Henan Province Eye Hospital, Zhengzhou, P.R. China.
  • 2 Chongqing Key Laboratory of Ophthalmology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Eye Institute, Chongqing Branch of National Clinical Research Center for Ocular Diseases, Chongqing, P.R. China.
  • 3 Southwest Hospital, Army Medical University, Chongqing, China.
  • 4 Department of Ophthalmology, Joint Research Laboratory for Ocular Immunology and Retinal Injury Repair, The First Affiliated Hospital of Zhengzhou University, Henan International, Henan Province Eye Hospital, Zhengzhou, P.R. China. peizengycmu@126.com.
  • # Contributed equally.
PMID: 39342514 DOI: 10.1007/s10753-024-02149-5
Abstract

Irisin, proteolytically cleaved from Fndc5 protein, has been identified as an exercise-related hormone. Here, we investigated the irisin levels in aqueous humor and its involvement in the pathogenesis of uveitis. The results revealed that the irisin level in the aqueous humor was significantly decreased in Vogt-Koyanagi-Harada (VKH), and Behcet uveitis (BU) patients, and was negatively correlated with TNF-α in BU patients. Exogenous supplementation of irisin alleviated scores of experimental autoimmune uveitis (EAU) clinically and pathologically and suppressed the proportion of Th1 and Th17 cells in spleen. Fndc5-/- EAU mice exhibited more severe inflammatory manifestations with increased microglial activation in the retina. Irisin could mitigate M1 microglia and promote M2 microglia polarization. RNA Sequencing of the retina showed that HIF-1α pathway was significantly enriched in Fndc5-/- EAU mice. HIF-1α pathway inhibitor significantly rescued EAU severity, associated with a decreased M1 microglial polarization in the retina of Fndc5-/- mice. In conclusion, we highlighted that irisin could alleviate uveitis by inhibiting Th1 and Th17 cells and reducing M1 microglial polarization via HIF-1α pathway.

Keywords

HIF-1α pathway; irisin; iveitis; microglia.

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