Mucosal-associated invariant T cells have therapeutic potential against ocular autoimmunity

• Published in: Mucosal immunology Vol. 15; no. 2; pp. 351 - 361
• Main Authors: Yamana, Satoshi, Shibata, Kensuke, Hasegawa, Eiichi, Arima, Mitsuru, Shimokawa, Shotaro, Yawata, Nobuyo, Takeda, Atsunobu, Yamasaki, Sho, Sonoda, Koh-Hei
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.02.2022
• Subjects: Animals; Antigens; Autoimmune diseases; Autoimmunity; Experimental autoimmune uveitis; Experimental autoimmune uveoretinitis; Eye - pathology; Humans; Inflammation; Interleukin 22; Lymphocytes T; Metabolites; Mice; Mucosa; Mucosal-Associated Invariant T Cells - metabolism; Neuroprotection; Pathology; Retina; Single-cell protein; Uveitis; Uveitis - metabolism; Uveitis - pathology; Uveomeningoencephalitic Syndrome; Visual perception
• ISSN: 1933-0219; 1935-3456
• DOI: 10.1038/s41385-021-00469-5

Autoimmune uveitis is a sight-threatening disease induced by pathogenic T cells that recognize retinal antigens; it is observed in disorders including Vogt-Koyanagi-Harada disease (VKH). The roles of specific T cell subsets and their therapeutic potential against autoimmune uveitis are not fully understood. Here we conducted multi-parametric single-cell protein quantification which shows that the frequency of CD161 TRAV1-2 mucosal-associated invariant T (MAIT) cells that recognize vitamin B2 metabolite-based antigens is decreased in relapsing VKH patients compared to individuals without active ocular inflammation. An experimental autoimmune uveitis (EAU) mouse model revealed that genetic depletion of MAIT cells reduced the expression of interleukin (Il) 22 and exacerbated retinal pathology. Reduced IL-22 levels were commonly observed in patients with relapsing VKH compared to individuals without active ocular inflammation. Both mouse and human MAIT cells produced IL-22 upon stimulation with their antigenic metabolite in vitro. An intravitreal administration of the antigenic metabolite into EAU mice induced retinal MAIT cell expansion and enhanced the expressions of Il22, as well as its downstream genes related to anti-inflammatory and neuroprotective effects, leading to an improvement in both retinal pathology and visual function. Taken together, we demonstrate that a metabolite-driven approach targeting MAIT cells has therapeutic potential against autoimmune uveitis.