Clarification of novel functions of the protein degradation system
Project/Area Number |
17K19568
|
Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
|
Allocation Type | Multi-year Fund |
Research Field |
Pathology, Infection/Immunology, and related fields
|
Research Institution | Wakayama Medical University |
Principal Investigator |
Kaisho Tsuneyasu 和歌山県立医科大学, 先端医学研究所, 教授 (60224325)
|
Co-Investigator(Kenkyū-buntansha) |
金澤 伸雄 和歌山県立医科大学, 医学部, 准教授 (90343227)
|
Project Period (FY) |
2017-06-30 – 2019-03-31
|
Project Status |
Completed (Fiscal Year 2018)
|
Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2017: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
|
Keywords | 炎症 / タンパク質分解 / 免疫プロテアソーム / 遺伝子変異 / プロテアソーム / 免疫異常 |
Outline of Final Research Achievements |
Proteasome is a protein complex and involved in cell or individual homeostasis by degrading unnecessary proteins. Genetic mutation of a proteasome subunit leads to refractory inflammations, called autoinflammatory diseases, but the underlying pathological mechanisms remain largely unknown. We have generated mutant mice carrying a novel genetic mutation of a proteasome subunit, which was found in an autoinflammatory patient and found multiple immune disorders in the mutant mice. The mutant mice are novel and quite useful for clarifying the pathogenesis of autoinflammatory diseases.
|
Academic Significance and Societal Importance of the Research Achievements |
単一遺伝子の変異によって難治性の炎症病態を来す自己炎症性疾患の病態を明らかにすることは、当該疾患ばかりでなく、がんや炎症など一般的な炎症病態の治療法の開発にも有用である。本研究では、自己炎症性疾患患者由来の新規の遺伝子変異を持つマウスを作成し、その変異が多彩な免疫異常をきたすユニークな表現型を呈することを明らかにした。この変異マウスの解析を進めることにより、炎症病態の新たなメカニズムを明らかになり、新規の炎症制御剤の開発に結び付く成果が期待される。
|
Report
(3 results)
Research Products
(94 results)
-
-
-
-
-
-
-
-
-
-
-
-
-
[Journal Article] A defined commensal consortium elicits CD8 T cells and anti-cancer immunity2019
Author(s)
T.Tanoue, S.Morita, D.R.Plichta, A.N.Skelly, W.Suda, Y.Sugiura, S.Narushima, H.Vlamakis, I.Motoo, K.Sugita, A.Shiota, K.Takeshita, K.Yasuma, D.Riethmacher, T.Kaisho, J.M.Norman, D.Mucida, M.Suematsu, T.Yaguchi, V.Bucci, T.Inoue, Y.Kawakami, B.Olle, B.Roberts, M.Hattori, R.J.Xavier, K.Atarashi, K.Honda
-
Journal Title
Nature
Volume: 565
Issue: 7741
Pages: 600-605
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[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
-
Journal Title
International Immunology
Volume: 印刷中
Issue: 10
Pages: 657-668
DOI
Related Report
Peer Reviewed / Open Access
-
[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
-
Journal Title
Journal of Investigative Dermatology
Volume: 印刷中
Issue: 6
Pages: 1329-1338
DOI
Related Report
Peer Reviewed / Open Access
-
-
[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
-
Journal Title
International Journal of Hematology
Volume: 印刷中
Issue: 6
Pages: 744-750
DOI
Related Report
Peer Reviewed / Open Access
-
[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
-
Journal Title
Cancer Science
Volume: 110
Issue: 4
Pages: 1279-1292
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
-
-
[Journal Article] Heme ameliorates dextran sodium sulfate-induced colitis through providing intestinal macrophages with noninflammatory profiles.2018
Author(s)
Kayama H, Kohyama M, Okuzaki D, Motooka D, Barman S, Okumura R, Muneta M, Hoshino K, Sasaki I, Ise W, Matsuno H, Nishimura J, Kurosaki T, Nakamura S, Arase H, Kaisho T, Takeda K.
-
Journal Title
Proc Natl Acad Sci U S A.
Volume: 115
Issue: 33
Pages: 8418-8423
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
-
-
-
-
[Journal Article] Novel PSTPIP1 gene mutation in pyoderma gangrenosum, acne and suppurative hidradenitis syndrome.2018
Author(s)
Saito N, Minami-Hori M, Nagahata H, Nozaki H, Iinuma S, Igawa S, Kanno K, Kishibe M, Kanazawa N, Ishida-Yamamoto A
-
Journal Title
Journal of Dermatology
Volume: in press
Issue: 8
DOI
Related Report
Peer Reviewed
-
-
-
-
-
-
-
-
-
[Journal Article] CD8+ T cells orchestrate pDC-XCR1+ dendritic cell spatial and functional cooperativity to optimize priming.2017
Author(s)
A. Brewitz, S. Eickhoff, S. Daehling, T. Quast, S. Bedoui, R. A. Kroczek, C. Kurts, N. Garbi, W. Barchet, M. Iannacone, F. Klauschen, W. Kolanus, T. Kaisho, M. Colonna, R. N. Germain, W. Kastenmueller.
-
Journal Title
Immunity
Volume: 46
Issue: 2
Pages: 205-219
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
[Journal Article] Development of a novel CD4+ TCR transgenic line that reveals a dominant role for CD8+ DC and CD40-Signaling in the generation of helper and CTL responses to blood stage malaria.2017
Author(s)
3.D. Fernandez-Ruiz, LS. Lau, N. Ghazanfari, ..names of 12 authors were removed,,, A. Cozijnsen, V. Mollard, AD. Uboldi, CJ. Tonkin, TF. de Koning-Ward, PR. Gilson, T. Kaisho, A. Haque, BS. Crabb, FR. Carbone, GI. McFadden, WR. Heath.
-
Journal Title
J. Immunol.
Volume: 199
Issue: 12
Pages: 4165-4179
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
-
-
-
-
-
-
-
-
-
-
[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回日本免疫学会総会・学術集会記録
Related Report
-
[Presentation] Cholera toxin B can induce interleukine-1β production in peritoneal macrophages through activation of pyrin inflammasome2018
Author(s)
Izumi Sasaki, Takashi Orimo, Hiroaki Hemmi, Toshiya Ozasa, Yuri Fukuda-Ohta, Mio Morinaka, Shinji Fukuda, Koichi Furukawa, Etsushi Kuroda, Ken J. Ishii, Tsuneyasu Kaisho
Organizer
第47回日本免疫学会総会・学術集会記録
Related Report
-
-
-
-
-
-
-
-
-
[Presentation] Analysis of mice carrying a novel mutation in a proteasome subunit gene identified in anautoinflammatory disease patient2018
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回日本免疫学会総会・学術集会記録
Related Report
-
-
-
-
[Presentation] Foxp3+ regulatory T cells are expanded by ultraviolet B-exposed PD-L1+ skin dendritic cell expressing a unique set of genes in a CSF1-independent manner2018
Author(s)
Sayuri Yamazaki, Mizuyu Odanaka, Hiroaki Shime, Masaki Imai, Akiko Nishioka, Saori Kasuya, Dieter Riethmacher, Hiroaki Hemmi, Tsuneyasu Kaisho, Naganari Ohkura, Shimon Sakaguchi, Akimichi Morita
Organizer
International Investigative Dermatology 2018
Related Report
Int'l Joint Research / Invited
-
-
[Presentation] Time-resolved systems analysis of virus infection fate regulation: the XCL1-XCR1 communication axis links T cell exhaustion with effector maintenance2018
Author(s)
J. Argilaguet, M. Pedragosa, A. Esteve-Codina, G. Riera, E. Vidal, C. Peligero-Cruz, D. Andreu, T. Kaisho, G. Bocharov, B. Ludewig, S. Heath, A. Meyerhans
Organizer
15th International Symposium on Dendritic Cells
Related Report
Int'l Joint Research
-
-
-
-
-
-
-
-
-
-
[Presentation] A Japanese family of PASH (pyoderma gangrenosum, acne and suppurative hidradenitis) syndrome with a distinct PSTPIP1 mutation and review of related syndromes, PAPA, PAMI, PAPASH, PsAPASH, PASS, and PAC2018
Author(s)
Kanazawa N, Saito N, Igawa S, Kishibe M, Ishida-Yamamoto A
Organizer
13th Meeting of the German-Japanese Society for Dermatology
Related Report
Int'l Joint Research
-
-
-
-
-
-
-
-
-
-
-