Poster Presentation CD1-MR1 Workshop 2025

TCR-dependent MAIT cell activation controls visual function (#117)

Kensuke Shibata 1 , Chihiro Fukui 2 , Yanqi Xue 2 , Satoshi Yamana 2 , Eiichi Hasegawa 2 , Nobuyo Yawata 3 , Sho Yamasaki 4 , Koh-Hei Sonoda 2
  1. Department of Visual Regeneration, Kyushu University, Fukuoka, Japan
  2. Department of Ophthalmology, Kyushu University, Fukuoka, Japan
  3. Department of Ocular Pathology and Imaging Science, Kyushu University, Fukuoka, Japan
  4. Department of Molecular Immunology, Osaka University, Suita, Osaka, Japan

The eye is the only organ responsible for visual function, yet the mechanism by which maintains its integrity is not well understood. Herein, studying an experimentally autoimmune uveitis (EAU) mouse model that accompanies reduced visual function, we observed that mucosal-associated invariant T (MAIT) cells have protective roles of visual function. Single cell analysis of EAU-induced retina and intravitreal administration experiments with MAIT cell agonist 5-OP-RU [5-(2-oxopropylideneamino)-6-D-ribitylaminouracil] and antagonist Acetyl-6-formylpterin (Ac-6-FP) to EAU mice showed involvement of TCR-dependent MAIT cell activation on this protective effect. Spatial transcriptomic analysis revealed that Wingless/int1(Wnt) signaling pathway-related genes were upregulated in the retina of EAU-induced mice in a MR1-dependent manner. Intravitreal administration of a Wnt signaling agonist improved visual function in EAU mice. These results reveal a protective immunological response mounted by MAIT cells in the eye.