TY - JOUR
T1 - Invariant natural killer T cells play dual roles in the development of experimental autoimmune uveoretinitis
AU - Satoh, Masashi
AU - Namba, Ken ichi
AU - Kitaichi, Nobuyoshi
AU - Endo, Noriko
AU - Kitamei, Hirokuni
AU - Iwata, Daiju
AU - Ohno, Shigeaki
AU - Ishida, Susumu
AU - Onoé, Kazunori
AU - Watarai, Hiroshi
AU - Taniguchi, Masaru
AU - Ishibashi, Tatsuro
AU - Stein-Streilein, Joan
AU - Sonoda, Koh Hei
AU - Van Kaer, Luc
AU - Iwabuchi, Kazuya
N1 - Funding Information:
We wish to thank Pharmaceutical Research Laboratories, Kirin Brewery Co. Ltd. for kindly providing α-galactosylceramide, Riken Institute for Integrative Medical Science (IMS; formerly Research Center for Allergy and Immunology; RCAI) for RCAI-56. We also acknowledge the NIH Tetramer Core Facility (contract HHSN272201300006C) for provision of I-A b and CD1d tetramers. This study was supported by a grant for Research on Behçet's Disease from The Ministry of Health, Labor, and Welfare (MHLW) , Japan (KI). M.S. is supported by a grant from The Parents' Association Grant of Kitasato University, School of Medicine (Keyaki Kai) and by a BioLegend/Tomy Digital Biology Research Grant.
Publisher Copyright:
© 2016 Elsevier Ltd
PY - 2016/12/1
Y1 - 2016/12/1
N2 - 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-Ab tetramers 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.
AB - 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-Ab tetramers 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.
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U2 - 10.1016/j.exer.2016.10.003
DO - 10.1016/j.exer.2016.10.003
M3 - Article
C2 - 27720708
AN - SCOPUS:84992126936
VL - 153
SP - 79
EP - 89
JO - Experimental Eye Research
JF - Experimental Eye Research
SN - 0014-4835
ER -