title: Invariant natural killer T cells play dual roles in the development of experimental autoimmune uveoretinitis.
abstract: Experimental autoimmune uveoretinitis (EAU) represents an experimental model for human endogenous uveitis, which is caused by Th1/Th17 cell-mediated inflammation. Natural killer T (NKT) cells recognize lipid antigens and produce large amounts of cytokines upon activation. To examine the role of NKT cells in the development of uveitis, EAU was elicited by immunization with a peptide from the human interphotoreceptor retinoid-binding protein (hIRBP1-20) in complete Freund's adjuvant and histopathology scores were evaluated in C57BL/6 (WT) and NKT cell-deficient mice. NKT cell-deficient mice developed more severe EAU pathology than WT mice. When WT mice were treated with ligands of the invariant subset of NKT cells (α-GalCer or RCAI-56), EAU was ameliorated in mice treated with RCAI-56 but not α-GalCer. IRBP-specific Th1/Th17 cytokines were reduced in RCAI-56-treated compared with vehicle-treated mice. Although the numbers of IRBP-specific T cells detected by hIRBP3-13/I-Abtetramers in the spleen and the draining lymph node were the same for vehicle and RCAI-56 treatment groups, RORγt expression by tetramer-positive cells in RCAI-56-treated mice was lower than in control mice. Moreover, the eyes of RCAI-56-treated mice contained fewer IRBP-specific T cells compared with control mice. These results suggest that invariant NKT (iNKT) cells suppress the induction of Th17 cells and infiltration of IRBP-specific T cells into the eyes, thereby reducing ocular inflammation. However, in sharp contrast to the ameliorating effects of iNKT cell activation during the initiation phase of EAU, iNKT cell activation during the effector phase exacerbated disease pathology. Thus, we conclude that iNKT cells exhibit dual roles in the development of EAU.
authors.affiliation: Department of Immunology, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Satoh
authors.affiliation: Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Ken-Ichi
authors.initials: KI
authors.lastname: Namba
authors.affiliation: Department of Ophthalmology, Health Sciences University of Hokkaido, Sapporo, Japan.
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Kitaichi
authors.affiliation: Department of Immunology, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Endo
authors.affiliation: Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Hirokuni
authors.initials: H
authors.lastname: Kitamei
authors.affiliation: Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Daiju
authors.initials: D
authors.lastname: Iwata
authors.affiliation: Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Ohno
authors.affiliation: Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Ishida
authors.affiliation: Division of Immunobiology, Research Section of Pathophysiology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Onoé
authors.affiliation: Center for Stem Cells and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST), Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watarai
authors.affiliation: RIKEN Research Center for Allergy and Immunology, Yokohama, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Taniguchi
authors.affiliation: Department of Ophthalmology, Faculty of Medicine, Kyushu University Graduate School of Medical Science, Fukuoka, Japan.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Ishibashi
authors.affiliation: Schepens Eye Research Institute, Harvard Medical School, Boston, MA, USA.
authors.forename: Joan
authors.initials: J
authors.lastname: Stein-Streilein
authors.affiliation: Department of Ophthalmology, Faculty of Medicine, Kyushu University Graduate School of Medical Science, Fukuoka, Japan; Department of Ophthalmology, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Koh-Hei
authors.initials: KH
authors.lastname: Sonoda
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Luc
authors.initials: L
authors.lastname: Van Kaer
authors.affiliation: Department of Immunology, Kitasato University School of Medicine, Sagamihara, Japan. Electronic address: akimari@kitasato-u.ac.jp.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Iwabuchi
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D015551:Autoimmunity; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000473:pathology; D012173:Retinitis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014605:Uveitis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D016207:Cytokines
keywords: Autoimmunity; EAU; NKT cells; Ocular inflammation; Th17