Analysis of the immunoproteasome function in innate immunity
Project/Area Number |
18K07071
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 49030:Experimental pathology-related
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Research Institution | Okayama University of Science (2019-2020) Wakayama Medical University (2018) |
Principal Investigator |
Hemmi Hiroaki 岡山理科大学, 獣医学部, 教授 (20451924)
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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 |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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Keywords | プロテアソーム / 自然免疫 / 樹状細胞 / 単球 / 遺伝子変異 / 免疫プロテアソーム / 自然免疫機構 |
Outline of Final Research Achievements |
The proteasome is a large protein complex involved in degradation of intracellular proteins, and plays important roles in not only maintenance of cellular homeostasis by degrading damaged and/or useless proteins, but also intracellular signal transduction and generation of antigen peptides. Genetic mutation in several proteasome subunit genes cause severe autoinflammatory diseases, called proteasome-associated autoinflammatory syndrome (PRAAS). However, its pathological mechanisms are largely unveiled. In this study, mutant mice, carrying a novel mutation found in a proteasome subunit gene from PRAAS-like patients, were analyzed. We found that the mutation affected monocyte and dendritic cell differentiation, in addition to impaired lymphocyte development and/or functions. This mutant mouse model is useful for analyzing physiological function of proteasome on innate immune cell differentiation as well as its pathological functions in PRAAS.
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Academic Significance and Societal Importance of the Research Achievements |
プロテアソームは、様々な細胞や組織の恒常性の維持だけでなく、がんや炎症など多彩な疾患にも関与している。プロテアソームを構成する分子に生じた遺伝子変異により発症するプロテアソーム関連自己炎症性疾患についてその病態を解明することは、当該疾患だけでなく、一般的な炎症病態の治療法の開発にも有用であると考えられる。本研究では、当該疾患患者由来の新規遺伝子変異を導入したマウスを解析し、これまで知られていなかった骨髄系細胞の分化障害を見いだした。本変異マウスの解析により、プロテアソームの生理的機能および炎症病態の新たなメカニズムが解明や新規の炎症病態制御剤の開発につながる成果が得られることが期待される。
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Report
(4 results)
Research Products
(35 results)
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[Journal Article] Radiation inducible MafB gene is required for thymic regeneration2021
Author(s)
Daiki Hashimoto, Jose Gabriel R. Colet, Aki Murashima, Kota Fujimoto, Yuko Ueda, Kentaro Suzuki, Taiju Hyuga, Hiroaki Hemmi, Tsuneyasu Kaisho, Satoru Takahashi, Yousuke Takahama and Gen Yamada1
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Journal Title
Scientific Reports
Volume: -
Issue: 1
Pages: 10439-10439
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] The mechanism of action of Spi-B in the transcriptional activation of the interferon-α4 gene.2020
Author(s)
R. Miyazaki, H. Saiga, T. Kato, T. Bakoshi, R. Senba, A. Shintani, M. Suzuki, K. Takao, I. Sasaki, A. Iizuka, M. Sugiyama, N. Iwami, Y. Fukuda-Ohta, H. Hemmi, T. Tanaka, M. Miyake, T. Kaisho, K. Hoshino.
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Journal Title
Biochem Biophys Res Commun.
Volume: 30;525
Issue: 2
Pages: 477-482
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Anticancer effects of chemokine-directed antigen delivery to a cross-presenting dendritic cell subset with immune checkpoint blockade2020
Author(s)
Mizumoto Y, Hemmi H, Katsuda M, Miyazawa M, Kitahata Y, Miyamoto A, Nakamori M, Ojima T, Matsuda K, Nakamura M, Hayata K, Fukuda-Ohta Y, Sugiyama M, Ohta T, Orimo T, Okura S, Sasaki I, Tamada K, Yamaue H, Kaisho T.
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Journal Title
British Journal of Cancer
Volume: 122
Issue: 8
Pages: 1185-1193
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Identification of a novel CCDC22 mutation in a patient with severe Epstein?Barr virus-associated hemophagocytic lymphohistiocytosis and aggressive natural killer cell leukemia2019
Author(s)
Yamashita Y, Nishikawa A, Iwahashi Y, Fujimoto M, Sasaki I, Mishima H, Kinoshita A, Hemmi H, Kanazawa N, Ohshima K, Imadome KI, Murata SI、Yoshiura KI, Kaisho T, Sonoki T, Tamura S
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Journal Title
International Journal of Hematology
Volume: 印刷中
Issue: 6
Pages: 744-750
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Hyperglycemia is associated with psoriatic inflammation in both humans and mice2019
Author(s)
Ikumi K, Odanaka M, Shime H, Imai M, Osaga S, Taguchi O, Nishida E, Hemmi H, Kaisho T, Morita A, Yamazaki S
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Journal Title
Journal of Investigative Dermatology
Volume: 印刷中
Issue: 6
Pages: 1329-1338
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Programmed cell death ligand 1 disruption by clustered regularly interspaced short palindromic repeats/Cas9‐genome editing promotes antitumor immunity and suppresses ovarian cancer progression2019
Author(s)
Yahata T, Mizoguchi M, Kimura A, Orimo T, Toujima S, Kuninaka Y, Nosaka M, Ishida Y, Sasaki I, Fukuda‐Ohta Y, Hemmi H, Iwahashi N, Noguchi T, Kaisho T, Kondo T, Ino K
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Journal Title
Cancer Science
Volume: 110
Issue: 4
Pages: 1279-1292
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Cholera toxin B induces interleukin-1β production from resident peritoneal macrophages through the pyrin inflammasome as well as the NLRP3 inflammasome2019
Author(s)
Orimo T, Sasaki I, Hemmi H, Ozasa T, Fukuda-Ohta Y, Ohta T, Morinaka M, Kitauchi M, Yamaguchi T, Sato Y, Tanaka T, Hoshino K, Katayama KI, Fukuda S, Miyake K, Yamamoto M, Satoh T, Furukawa K, Kuroda E, Ishii KJ, Takeda K, Kaisho T
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Journal Title
International Immunology
Volume: 印刷中
Issue: 10
Pages: 657-668
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Generation and Analysis of Mice Carrying a Novel Heterozygous Missense Mutation of a Proteasome Subunit, PSMB9, in Patients with Autoinflammation and Immunodeficienty.2019
Author(s)
H. Hemmi, N. Kanazawa, N. Kinjo, S. Hamada, H. Ohnishi, T. Mizushima, A. Kinoshita, K.-I. Yoshiura, T. Kaisho.
Organizer
10th International congress 2019, Biannual Meeting of the International Society of Systemic Auto Inflammatory Diseases
Related Report
Int'l Joint Research
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[Presentation] A Case of Neonatal-onset Proteasome-associated Autoinflammation and Immunodeficiency Disease Resembling but Distinct from Nakajo-Nishinura Syndrome.2019
Author(s)
N. Kinjo, S. Hamada, K. Nakanishi, H. Mishima, A. Kinoshita, K.-I. Yoshiura, T. Mizushima, J. Hamazaki, S. Murata, H. Hemmi, T. Kaisho, N. Kanazawa.
Organizer
10th International congress 2019, Biannual Meeting of the International Society of Systemic Auto Inflammatory Diseases
Related Report
Int'l Joint Research
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[Presentation] Novel proteasome-related autoinflammation and immunodeficiency disease caused by a distinct heterozygous missense mutation in the PSMB9 gene.2019
Author(s)
Nobuo Kanazawa, Yumi Nakatani, Yutaka Inaba, Kayo Kunimoto, Noriko Kinjo, Satoru Hamada, Tsunehiro Mizushima, Akira Kinoshita, Koh-Ichiro Yoshiura, Jun Hamazaki, Shigeo Murata, Hidenori Ohnishi, Takashi Orimo, Hiroaki Hemmi, Tsuneyasu Kaisho.
Organizer
日本研究皮膚科学会 第44回年次学術大会
Related Report
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[Presentation] Defective dendritic cell and monocyte development in proteasome subunit mutant mice.2019
Author(s)
Hemmi H, Orimo T, Sasaki I, Kato T, Fukuda-Ohta Y, Kinjo N, Hamada S, Kinoshita A, Yoshiura KI, Ohnishi H, Kanazawa N, Kaisho T.
Organizer
第48回日本免疫学会学術集会
Related Report
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[Presentation] Analysis of mice carrying a novel mutation in a proteasome subunit gene identified in an autoinflammatory disease patient.2018
Author(s)
Toshiya Ozasa, Hiroaki Hemmi, Akira Kinoshita, Takashi Kato, Takashi Orimo, Izumi Sasaki, Yuri Fukuda-Ohta, Noriko Kinjo, Koh-Ichiro Yoshiura, Tsunehiro Mizushima, Nobuo Kanazawa, Tsuneyasu Kaisho
Organizer
第47回日本免疫学会学術集会
Related Report
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[Presentation] Impaired development of dendritic cells in proteasome subunit mutant mice2018
Author(s)
Hiroaki Hemmi, Toshiya Ozasa, Akira Kinoshita, Takashi Kato, Takashi Orimo, Izumi Sasaki, Yuri Fukuda-Ohta, Noriko Kinjo, Koh-Ichiro Yoshiura, Tsunehiro Mizushima, Nobuo Kanazawa, Tsuneyasu Kaisho
Organizer
第47回日本免疫学会学術集会
Related Report
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