The altered immune response caused by CCDC22 mutation and its association with EBV-HLH development and severity.
Project/Area Number |
20K17405
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 54010:Hematology and medical oncology-related
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Research Institution | Wakayama Medical University |
Principal Investigator |
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Keywords | CCDC22 / EBV-HLH / NFκB |
Outline of Research at the Start |
EBウイルス関連血球貪食症候群(EBV-HLH)は, EBV感染が引き金となって過剰な炎症が生じ, 汎血球減少と臓器障害を呈する全身性炎症性疾患である. 発症には, EBV感染細胞に対する宿主の病的免疫応答が関わっているが, その詳細は不明である. 申請者はEBV-HLH患者にNFκB経路を制御するCCDC22の新規遺伝子変異を同定した. CCDC22変異によるNFκB制御の変調がEBV-HLHの病態に関与していると予想され, CCDC22の機能解析を行い, CCDC22変異のEBV-HLHにおける役割を検討する.
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Outline of Final Research Achievements |
We conducted a functional analysis of the CCDC22V38M mutation, which was identified in a patient with severe EBV-HLH. NFκB activity was unaffected by forced expression of CCDC22 in HEK293T cells. However, the V38M mutation altered its intracellular localization. Knockdown of CCDC22 in Neuro2a cells resulted in impaired neuronal differentiation. CCDC22V38M mice did not significantly differ from wild type in their natural course. RNAseq of MEFs revealed alterations in the expressions of cytokine- and chemokine-related gene. Although this study does not establish a direct link between the CCDC22V38M mutation and the development of HLH, it suggests that CCDC22 plays an important role in the functioning of the nervous and immune systems.
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Academic Significance and Societal Importance of the Research Achievements |
本研究では、難治性疾患であるEBV-HLHの重症例より同定したCCDC22新規遺伝子変異の解析を行った。本研究ではCCDC22の免疫系への関与が示唆される新知見が得られた。CCDC22については、NFκBの調節因子であることや、タンパクの細胞内輸送に関わることなど報告されているものの、まだ機能は十分に解明されていない。本研究成果を足がかりにCCDC22の機能解析が進めば、免疫系の新たな調節機構の解明や、EBV-HLHの病態解明に貢献できる可能性がある。
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Report
(4 results)
Research Products
(14 results)
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[Journal Article] Erdheim-Chester disease diagnosed with right atrium tumors2021
Author(s)
Takeda S, Murata S, Tane M, Yoshida K, Iwamoto R, Warigaya K, Sakaki A, Yokoya Y, Tanaka K, Tochino Y, Yamashita Y, Hosoi H, Mushino T, Nishikawa A, Tamura S, Sonoki T.
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Journal Title
Rinsho Ketsueki
Volume: 62
Pages: 91-93
NAID
Related Report
Peer Reviewed
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[Journal Article] Heterozygous missense variant of the proteasome subunit β-type 9 causes neonatal-onset autoinflammation and immunodeficiency2021
Author(s)
Kanazawa N, Hemmi H, Kinjo N, Ohnishi H, Hamazaki J, M.H, K.A, M.T, H.S, K.N, K.S, H.Y, I.K, N.R, T.M, Y.Y, T.S, O.T, O.T, K.T, S.I, F.Y, W.N, I.Y, K.K, O.S, T.T, N.K, M.S, Y.K, Kaisho T
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Journal Title
Nature Communications
Volume: 12
Issue: 1
Pages: 0-0
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Targeting Adaptive IRE1α Signaling and PLK2 in Multiple Myeloma: Possible Anti-Tumor Mechanisms of KIRA8 and Nilotinib.2020
Author(s)
Yamashita Y, Morita S, Hosoi H, Kobata H, Kishimoto S, Ishibashi T, Mishima H, Kinoshita A, Backes BJ, Yoshiura KI, Papa FR, Sonoki T, Tamura S
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Journal Title
Int J Mol Sci.
Volume: Aug 31;21(17)
Issue: 17
Pages: 6314-6314
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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