Genetics and immunity of NK cells in CMV-associated anterior uveitis
| Project/Area Number |
18K09467
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 56060:Ophthalmology-related
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| Research Institution | Kyushu University (2019-2020)
Fukuoka Dental College (2018) |
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Principal Investigator |
Yawata Nobuyo 九州大学, 医学研究院, 准教授 (90315812)
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| 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)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| 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)
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| 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 |
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| 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.
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| 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。
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Report
(4 results)
Research Products
(43 results)
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[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
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Journal Title
J Immunol
Volume: 8
Issue: 8
Pages: 2640-2655
DOI
Related Report
Peer Reviewed
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[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
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