Blockade of Interleukin-6 Signaling Suppresses Not Only Th17 but Also Interphotoreceptor Retinoid Binding Protein–Specific Th1 by Promoting Regulatory T Cells in Experimental Autoimmune Uveoretinitis

DOI Web Site PubMed 被引用文献5件 オープンアクセス
  • Hiroshi Haruta
    From the Department of Ophthalmology, Osaka University Graduate School of Medicine, Osaka, Japan; the 2Laboratory for Immune Signal, National Institute of Biomedical Innovation, Osaka, Japan;
  • Nobuyuki Ohguro
    From the Department of Ophthalmology, Osaka University Graduate School of Medicine, Osaka, Japan;
  • Minoru Fujimoto
    the Laboratory for Immune Signal, National Institute of Biomedical Innovation, Osaka, Japan;
  • Satoshi Hohki
    From the Department of Ophthalmology, Osaka University Graduate School of Medicine, Osaka, Japan; the 2Laboratory for Immune Signal, National Institute of Biomedical Innovation, Osaka, Japan;
  • Fumitaka Terabe
    the Laboratory for Immune Signal, National Institute of Biomedical Innovation, Osaka, Japan;
  • Satoshi Serada
    the Laboratory for Immune Signal, National Institute of Biomedical Innovation, Osaka, Japan;
  • Shintaro Nomura
    the Department of Animal Bioscience, Nagahama Institute of Bio-Science and Technology, Shiga, Japan; and
  • Kohji Nishida
    From the Department of Ophthalmology, Osaka University Graduate School of Medicine, Osaka, Japan;
  • Tadamitsu Kishimoto
    the Laboratory of Immune Regulation, Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan.
  • Tetsuji Naka
    the Laboratory for Immune Signal, National Institute of Biomedical Innovation, Osaka, Japan;

この論文をさがす

説明

PURPOSE. Both Th17 and Th1 cells contribute to experimental autoimmune uveoretinitis (EAU). Interleukin-6 (IL-6) blockade inhibits Th17 differentiation in EAU and potently suppresses ocular inflammation, although its effect on Th1 cells is unknown. To clarify the mechanism of IL-6 blockade, the authors investigated T helper cells with particular focus on Th1 and regulatory T cells (Treg) in EAU of IL-6 gene knockout (KO) mice. METHODS. EAU was induced in wild-type (WT) mice and in mice lacking IL-6 (IL-6KO), IL-17 (IL-17KO), and IFN-γ (GKO) on a C57BL/6 background. Clinical scores of EAU, cytokine levels in supernatants from ocular tissue homogenates, and T helper cell differentiation in lymph nodes in each mouse were examined. To study the roles of Treg cells, EAU was induced in IL-6KO mice treated with anti-CD25 monoclonal antibody (mAb) to deplete Treg cells in vivo. RESULTS. Inflammation was comparable between WT, IL-17KO, and GKO mice but was absent in IL-6KO mice. Th17 and interphotoreceptor retinoid binding protein (IRBP)-specific Th1 cells were increased in GKO and IL-17KO mice, respectively, whereas both populations were reduced in IL-6KO mice. Th1-dominant EAU in IL-17KO mice was suppressed by anti-IL-6R mAb treatment. Treg cell depletion in vivo induced EAU in IL-6KO mice. CONCLUSIONS. After the induction of EAU, IL-6 deficiency resulted in the inhibition of the IRBP-specific Th1 response and enhanced the generation of IRBP-specific Treg cells. Furthermore, Treg was needed to inhibit Th1 responses and ocular inflammation in IL-6KO mice. Protective effects of IL-6 signaling blockade in EAU involve not only Th17 cell inhibition but also IRBP-specific Treg cell promotion.

収録刊行物

被引用文献 (5)*注記

もっと見る

関連プロジェクト

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ