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Genetics and immunity of NK cells in CMV-associated anterior uveitis

Research Project

Project/Area Number 18K09467
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56060:Ophthalmology-related
Research InstitutionKyushu University (2019-2020)
Fukuoka Dental College (2018)

Principal Investigator

Yawata Nobuyo  九州大学, 医学研究院, 准教授 (90315812)

Co-Investigator(Kenkyū-buntansha) 園田 康平  九州大学, 医学研究院, 教授 (10294943)
川野 庸一  福岡歯科大学, 口腔歯学部, 教授 (90211185)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsサイトメガロウイルス / NK細胞 / KIR / ぶどう膜炎 / HLA / サイトメガロウイルス前部ぶどう膜炎 / HLA class I / NKG2C / KLRG1 / CD57 / HLA ligand / NK細胞サブセット / 分化マーカー
Outline of Final Research Achievements

Cytomegalovirus (CMV) causes clinical issues in immunocompromised hosts. CMV-associated anterior uveitis (CMV-AU) is a new disease entity manifesting recurrent ocular inflammation in immunocompetent individuals, especially in Asian populations after middle age. We first characterized Killer cell Immunoglobulin-like Receptors (KIR) and HLA class I that encode differences in human NK cell responses in CMV-AU patients and analyzed NK cell profiles with CMV-related markers. We have found that KIR3DL1 and HLA class I combinations encoding strong receptor-ligand interactions were present at substantially higher frequencies in CMV-AU. NK cell profiling in these cases revealed expansion of the subset co-expressing CD57, KLRG1, and the CMV-recognizing NKG2C receptor. The findings imply that a mechanism of CMV-AU pathogenesis likely involves NK cells co-expressing CD57/KLRG1/NKG2C that develop on a genetic background of KIR3DL1/HLA-B allotypes encoding strong receptor-ligand interactions.

Academic Significance and Societal Importance of the Research Achievements

サイトメガロウイルスは世界人口の50-90%に潜伏感染し、これまでエイズ患者や臓器移植後などの高度の免疫低下状態でのみサイトメガロウイルス網膜炎などの感染症が起こると考えられていた。近年明らかになったサイトメガロウイルス前部ぶどう膜炎は明らかな免疫低下のない患者にみられる新たな疾患で、アジア人に多く発症しているがその発症メカニズムは明らかでない。本研究ではホストの免疫遺伝学的背景とサイトメガロウイルスのコントロールに重要なナチュラルキラー細胞の疾患特徴的なプロファイルを明らかにした。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (43 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (3 results) Journal Article (10 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 8 results,  Open Access: 5 results) Presentation (28 results) (of which Int'l Joint Research: 11 results) Book (1 results) Remarks (1 results)

  • [Int'l Joint Research] Singapore Eye Research Institute/National University of Singapore/Duke-NUS Medical School(シンガポール)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Singapore Eye Research Institute/Singapore National Eye Centre/National University of Singapore(シンガポール)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] Singapore Eye Research Institute/National University of Singapore/Duke-NUS Medical School(シンガポール)

    • Related Report
      2018 Research-status Report
  • [Journal Article] Molecular Signatures of Natural Killer Cells in CMV-Associated Anterior Uveitis, A New Type of CMV-Induced Disease in Immunocompetent Individuals2021

    • Author(s)
      Yawata Nobuyo、Shirane Mariko、Woon Kaing、Lim Xinru、Tanaka Hidenori、Kawano Yoh-Ichi、Yawata Makoto、Chee Soon-Phaik、Siak Jay、Sonoda Koh-Hei
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 7 Pages: 3623-3623

    • DOI

      10.3390/ijms22073623

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Vitreous levels of interleukin-35 as a prognostic factor in B-cell vitreoretinal lymphoma2020

    • Author(s)
      Takeda Atsunobu、Hasegawa Eiichi、Nakao Shintaro、Ishikawa Keijiro、Murakami Yusuke、Hisatomi Toshio、Arima Mitsuru、Yawata Nobuyo、Oda Yoshinao、Kimura Kazuhiro、Yoshikawa Hiroshi、Sonoda Koh-Hei
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 15715-15715

    • DOI

      10.1038/s41598-020-72962-z

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Singapore Ocular Tuberculosis Immunity Study (SPOTIS): Role of T-lymphocyte Profiling in Patients with Presumed Ocular Tuberculosis2020

    • Author(s)
      Hutchinson Paul E.、Kee Ae Ra、Agrawal Rupesh、Yawata Nobuyo、Tumulak Mayjane Jg、Connolly John E.、Chee Soon-Phaik、Siak Jay
    • Journal Title

      Ocular Immunology and Inflammation

      Volume: 14 Issue: 7-8 Pages: 1-7

    • DOI

      10.1080/09273948.2020.1767791

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Kinetics of Tear Fluid Proteins after Endothelial Keratoplasty and Predictive Factors for Recovery from Corneal Haze2019

    • Author(s)
      Yawata Nobuyo、Awate Sunita、Liu Yu-Chi、Yuan Shi、Woon Kaing、Siak Jay、Kawano Yoh-Ichi、Sonoda Koh-Hei、Mehta Jodhbir S.、Yawata Makoto
    • Journal Title

      Journal of Clinical Medicine

      Volume: 9 Issue: 1 Pages: 63-63

    • DOI

      10.3390/jcm9010063

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Assessment of clinical signs associated with adenoviral epidemic keratoconjunctivitis cases in southern Japan between 2011 and 20142019

    • Author(s)
      Aoki Koki、Gonzalez Gabriel、Hinokuma Rikutaro、Yawata Nobuyo、Tsutsumi Masayuki、Ohno Shigeaki、Kitaichi Nobuyoshi
    • Journal Title

      Diagnostic Microbiology and Infectious Disease

      Volume: 95 Issue: 4 Pages: 114885-114885

    • DOI

      10.1016/j.diagmicrobio.2019.114885

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] The effectiveness of adalimumab treatment for non-infections uveitis.2019

    • Author(s)
      Hasegawa E, Takeda A, Yawata N, Sonoda KH.
    • Journal Title

      Immunol Med.

      Volume: 42 Issue: 2 Pages: 79-83

    • DOI

      10.1080/25785826.2019.1642080

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Challenges in management of epidemic keratoconjunctivitis with emerging recombinant human adenoviruses2019

    • Author(s)
      Gonzalez Gabriel、Yawata Nobuyo、Aoki Koki、Kitaichi Nobuyoshi
    • Journal Title

      Journal of Clinical Virology

      Volume: 112 Pages: 1-9

    • DOI

      10.1016/j.jcv.2019.01.004

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 【夏に多い疾患の診療】感染症 流行性角結膜炎2019

    • Author(s)
      瀧瑠美子, 八幡信代, 園田康平
    • Journal Title

      臨牀と研究

      Volume: 96 Pages: 39-44

    • Related Report
      2019 Research-status Report
  • [Journal Article] 【ぶどう膜炎の治療アップデート】オーダーメイド治療への展開2019

    • Author(s)
      八幡信代
    • Journal Title

      眼科グラフィック

      Volume: 8 Pages: 600-605

    • Related Report
      2019 Research-status Report
  • [Journal Article] Different Selected Mechanisms Attenuated the Inhibitory Interaction of KIR2DL1 with C2+ HLA-C in Two Indigenous Human Populations in Southern Africa2018

    • Author(s)
      Nemat-Gorgani N, Hilton HG, Henn BM, Lin M, Gignoux CR, Myrick JW, Werely CJ, Granka JM, Moller M, Hoal EG, Yawata M, Yawata N, Boelen L, Asquith B, Parham P, Norman PJ
    • Journal Title

      J Immunol

      Volume: 8 Issue: 8 Pages: 2640-2655

    • DOI

      10.4049/jimmunol.1701780

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] サイトメガロウイルス関連ぶどう膜炎のウイルスタンパクUL40多型解析2021

    • Author(s)
      白根 茉利子、八幡 信代、山名 智志、林田 陽、蕪城 俊克、柴田 健輔、伊東 崇子、長谷川 英一、武田 篤信、園田 康平
    • Organizer
      日本眼科学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Polymorphisms of cytomegalovirus UL40 protein signal peptides in Cytomegalovirus-associated uveitis2021

    • Author(s)
      Mariko Shirane, Nobuyo Yawata, Satoshi Yamana, Akira Hayashida, Takako Ito, Toshikatsu Kaburaki, Kensuke Shibata, Eiichi Hasegawa, Atsunobu Takeda, Koh-Hei Sonoda
    • Organizer
      Association for Research in Vision and Ophthalmology Annual conference
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ベーチェット病眼炎症発作に関連する末梢血単核球プロファイルのMass Cytometry解析2020

    • Author(s)
      八幡信代, 山名智志, 清田章文, 白根茉利子, 林田陽, 伊東崇子, 長谷川英一, 柴田健輔, 武田篤信, 滝澤仁, 園田康平
    • Organizer
      臨床免疫学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Mass Cytometry analysis of peripheral blood profiles associated with ocular inflammation in Behet disease2020

    • Author(s)
      Yawata N, Yamana S, Shibata K, Akifumi Kiyota, Shirane M, Hayashida A, Takeda A, Hitoshi Takizawa, Hasegawa E, Sonoda KH
    • Organizer
      2020 Joint meeting of Korea-China-Japan Ophthalmologists
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Behet病眼炎症に関連する末梢血中免疫サブセットのMass cytometry解析2020

    • Author(s)
      八幡信代, 山名智志, 柴田健輔, 清田章文, 白根茉利子, 林田陽, 武田篤信, 滝澤仁, 長谷川英一, 園田康平
    • Organizer
      日本眼科学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] High-dimensional immune cell profiling characterizes features of peripheral NK cell repertoires in CMV anterior uveitis2019

    • Author(s)
      Yawata N, Jay S, Kaing W, Xinru L, Soon Phaik Chee, Yawata M, Kawano Y, Sonoda KH
    • Organizer
      Association for Research in Vision and Ophthalmology 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Long term outcomes of infliximab in patients with Behcet’s disease-related uveitis2019

    • Author(s)
      Yamana S, Hasegawa E, Takeda A, Yawata N, Sonoda KH
    • Organizer
      Association for Research in Vision and Ophthalmology 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Outcomes of the treatment for refractory non-infectious uveitis with Adalimumab2019

    • Author(s)
      Hasegawa E, Yamana S, Yawata N, Takeda A, Sonoda KH
    • Organizer
      Global Ocular Inflammation Workshops 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Immune cell profiling in CMV anterior uveitis identifies NK cell subsets with CMV response potential2019

    • Author(s)
      Yawata N, Siak J, Chee SP, Yawata M, Kawano Y, Sonoda KH
    • Organizer
      Global Ocular Inflammation Workshops 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Effectiveness of treatment with Adalimumab in refractory non-infectious uveitis2019

    • Author(s)
      Hasegawa E, Yamana S, Yawata N, Takeda A, Sonoda KH
    • Organizer
      The 12th Joint Meeting of Chinese-Japanese-Korean ophthalmologists
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] High-dimensional immune cell profiling characterizes features of peripheral NK cell subsets in CMV anterior uveitis2019

    • Author(s)
      Yawata N, Siak J, Chee SP, Sonoda KH
    • Organizer
      The 12th Joint Meeting of Chinese-Japanese-Korean ophthalmologists
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Genetic profiles of Killer cell Immunoglobulin-like Receptors and ligands in patients with Cytomegalovirus Anterior Uveitis2019

    • Author(s)
      Yawata N, Siak J, Chee SP, Kawano Y, Yawata M, Sonoda KH
    • Organizer
      15th International Ocular Inflammation Society Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Risk factors associated with persistent ocular inflammation in patients with Vogt-Koyanagi-Harada disease2019

    • Author(s)
      Yamana S, Hasegawa E, Takeda A, Yawata N, Sonoda KH
    • Organizer
      15th International Ocular Inflammation Society Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] A case of adult T-cell leukemia presenting with scleritis2019

    • Author(s)
      Hasegawa E, Yamana S, Yawata N, Takeda A, Sonoda KH
    • Organizer
      15th International Ocular Inflammation Society Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 強膜炎をきっかけに診断がついた成人T細胞性白血病の1例2019

    • Author(s)
      長谷川英一, 山名智志, 八幡信代, 武田篤信, 園田康平
    • Organizer
      日本眼炎症学会
    • Related Report
      2019 Research-status Report
  • [Presentation] CMV前部ぶどう膜炎患者のKiller Cell Immunoglobulin-like Receptorリガンドの解析2019

    • Author(s)
      八幡信代, Siak J, 田中秀則, 小島裕人, Chee SP, 川野庸一, 園田康平
    • Organizer
      日本眼炎症学会
    • Related Report
      2019 Research-status Report
  • [Presentation] フォークト- 小栁-原田病患者における慢性化に関する因子の検討2019

    • Author(s)
      山名智志, 長谷川英一, 八幡信代, 武田篤信, 園田康平
    • Organizer
      日本眼炎症学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 眼内悪性リンパ腫とT細胞関連制御性サイトカインの関与2019

    • Author(s)
      武田篤信, 長谷川英一, 柴田健輔, 石川桂二郎, 木村和博, 吉田茂生, 八幡信代, 吉川洋, 園田康平
    • Organizer
      日本眼炎症学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 九州大学におけるサイトメガロ角膜内皮炎に対するガンシクロビル点眼治療2019

    • Author(s)
      岡村美砂子, 長谷川英一, 石川桂二郎, 八幡信代, 山名智志, 中尾新太郎, 疋田伸一, 武田篤信, 園田康平
    • Organizer
      日本眼炎症学会
    • Related Report
      2019 Research-status Report
  • [Presentation] サイトメガロウイルスによる慢性網膜壊死の2症例2019

    • Author(s)
      福嶋正俊, 吉富景子, 納富昭司, 向野利一郎, 八幡信代, 長谷川英一, 園田康平
    • Organizer
      六大学合同眼科研究会
    • Related Report
      2019 Research-status Report
  • [Presentation] サイトメガロウイルス前部ぶどう膜炎患者のKiller Cell Immunoglobulin-like Receptorとリガンドの解析2019

    • Author(s)
      八幡信代, Siak J, 田中秀則, 小島裕人, Chee Soon-Phaik, 川野庸一, 八幡真人, 園田康平
    • Organizer
      日本組織適合性学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] MTX・JAK阻害剤併用中に非典型的サイトメガロウイルス網膜炎を発症した1例2019

    • Author(s)
      長谷川英一, 八幡信代, 山名智志, 納富昭司, 向野利一郎, 園田康平
    • Organizer
      日本臨床免疫学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] サイトメガロウイルスによる慢性網膜壊死の2症例2019

    • Author(s)
      福嶋正俊, 吉富景子, 納富昭司, 向野利一郎, 八幡信代, 長谷川英一, 園田康平
    • Organizer
      日本臨床眼科学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 九大眼科における小児ぶどう膜炎の特徴2019

    • Author(s)
      福田洋輔, 長谷川英一, 山名智志, 白根茉利子, 武田篤信, 八幡信代, 園田康平
    • Organizer
      九州大学眼科研究会
    • Related Report
      2019 Research-status Report
  • [Presentation] Kinetics of Bilateral Tear Fluid Proteins After Endothelial Keratoplasty2018

    • Author(s)
      N Yawata, S Awate, YC Liu, S Yuan, J Siak, G Daston, J. S. Mehta, M Yawata
    • Organizer
      第122回日本眼科学会
    • Related Report
      2018 Research-status Report
  • [Presentation] Kinetics of Bilateral Tear Fluid Proteins After Endothelial Keratoplasty2018

    • Author(s)
      N Yawata, S Awate, YC Liu, S Yuan, J Siak, G Daston, J. S. Mehta, M Yawata
    • Organizer
      The Association for Research in Vision and Ophthalmology Annual meeting 2018
    • Related Report
      2018 Research-status Report
  • [Presentation] サイトメガロウイルス関連前部ぶどう膜炎患者末梢血NK細胞の解析2018

    • Author(s)
      八幡信代、Jay Siak、Soon-Phaik Chee、川野庸一、園田康平
    • Organizer
      第52回眼炎症学会
    • Related Report
      2018 Research-status Report
  • [Presentation] High-dimensional immune cell profiling reveals distinct NK subset responsive against CMV pp65 and associated with CMV anterior uveitis2018

    • Author(s)
      Nobuyo Yawata, Jay Siak, Soon-Phaik Chee, Makoto Yawata, Yoichi Kawano, Ko-hei Sonoda
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Research-status Report
  • [Book] ぶどう膜炎診療のストラテジー2020

    • Author(s)
      八幡信代, 園田康平
    • Total Pages
      300
    • Publisher
      三輪書店
    • ISBN
      9784895906906
    • Related Report
      2020 Annual Research Report
  • [Remarks] 九州大学医学部眼科 研究業績

    • URL

      http://www.eye.med.kyushu-u.ac.jp/class/results/index.php

    • Related Report
      2019 Research-status Report

URL: 

Published: 2018-04-23   Modified: 2022-12-28  

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