title: The Role of Interleukin-22 and Its Receptor in the Development and Pathogenesis of Experimental Autoimmune Uveitis.
abstract: IL-22 is a pro- and anti-inflammatory cytokine that is mainly produced by T cells and NK cells. Recent studies have reported the increased number of IL-22 producing T cells in patients with autoimmune noninfectious uveitis; however, the correlation between IL-22 and uveitis remains unclear. In this study, we aimed to determine the specific role of IL-22 and its receptor in the pathogenesis of uveitis. Serum concentration of IL-22 was significantly increased in uveitis patients. IL-22Rα was expressed in the retinal pigment epithelial cell line, ARPE-19. To examine the effect of IL-22, ARPE-19 was treated with recombinant IL-22. The proliferation of ARPE-19 and the production of monocyte chemoattractant protein (MCP)-1 from ARPE-19 were clearly elevated. IL-22 induced MCP-1 which facilitated the migration of inflammatory cells. Moreover, IL-22 increased the IL-22Rα expression in ARPE-19 through the activation of PI3K/Akt. Experimental animal models of uveitis induced by interphotoreceptor retinoid binding protein 1-20 (IRBP1-20) exhibited elevation of hyperplasia RPE and IL-22 production. When CD4+ T cells from the uveitis patients were stimulated with IRBP1-20, the production of IL-22 definitely increased. In addition, we examine the regulatory role of cysteamine, which has an anti-inflammatory role in the cornea, in uveitis through the down-regulation of IL-22Rα expression. Cysteamine effectively suppressed the IRBP1-20-induced IL-22Rα expression and prevented the development of IRBP1-20-induced uveitis in the experimental animal model. These finding suggest that IL-22 and its receptor have a crucial role in the development and pathogenesis of uveitis by facilitating inflammatory cell infiltration, and that cysteamine may be a useful therapeutic drug in treating uveitis by down-regulating IL-22Rα expression in RPE.
authors.affiliation: Department of Anatomy, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Yejin
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Republic of Korea.|Rheumatology Institute and Research for Sensory Organs Institute, Medical Research Center, Seoul National University, Seoul, Republic of Korea.|Department of Ophthalmology, Seoul Metropolitan Government Seoul National University, Boramae Medical Center, Seoul, Republic of Korea.
authors.forename: Tae Wan
authors.initials: TW
authors.lastname: Kim
authors.affiliation: Department of Anatomy, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Yun Seong
authors.initials: YS
authors.lastname: Park
authors.affiliation: Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Eui Man
authors.initials: EM
authors.lastname: Jeong
authors.affiliation: Department of Anatomy, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Dong-Sup
authors.initials: DS
authors.lastname: Lee
authors.affiliation: Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: In-Gyu
authors.initials: IG
authors.lastname: Kim
authors.affiliation: Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hum
authors.initials: H
authors.lastname: Chung
authors.affiliation: Department of Anatomy, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Young-Il
authors.initials: YI
authors.lastname: Hwang
authors.affiliation: Department of Anatomy, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Wang Jae
authors.initials: WJ
authors.lastname: Lee
authors.affiliation: Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hyeong Gon
authors.initials: HG
authors.lastname: Yu
authors.affiliation: Department of Anatomy, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jae Seung
authors.initials: JS
authors.lastname: Kang
mesh_terms: D000328:Adult; D000818:Animals; D016022:Case-Control Studies; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018932:Chemokine CCL2 / Q000378:metabolism; D003543:Cysteamine / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D025461:Feedback, Physiological; D005260:Female; D006801:Humans; D006965:Hyperplasia; D007378:Interleukins / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018123:Receptors, Interleukin / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D014605:Uveitis / Q000097:blood / Q000378:metabolism* / Q000473:pathology*; D000097043:Interleukin-22
chemical_list: D018932:Chemokine CCL2; D003543:Cysteamine; D007378:Interleukins; D018123:Receptors, Interleukin; D011994:Recombinant Proteins; D000097043:Interleukin-22; C415369:interleukin-22 receptor