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Analysis of the immunoproteasome function in innate immunity

Research Project

Project/Area Number 18K07071
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49030:Experimental pathology-related
Research InstitutionOkayama 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)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
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)
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.

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。

Report

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

    (35 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (1 results) Journal Article (9 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 8 results,  Open Access: 8 results) Presentation (25 results) (of which Int'l Joint Research: 8 results,  Invited: 2 results)

  • [Int'l Joint Research] the Johannes Gutenberg University Mainz(ドイツ)

    • Related Report
      2018 Research-status Report
  • [Journal Article] Immunogenic tumor cell death promotes dendritic cell migration and inhibits tumor growth via enhanced T cell immunity2021

    • Author(s)
      Moriya Taiki、Kitagawa Kurumi、Hayakawa Yuuki、Hemmi Hiroaki、Kaisho Tsuneyasu、Ueha Satoshi、Ikebuchi Ryoyo、Yasuda Ippei、Nakanishi Yasutaka、Honda Tetsuya、Matsushima Koji、Kabashima Kenji、Ueda Mizuki、Kusumoto Yutaka、Chtanova Tatyana、Tomura Michio
    • Journal Title

      iScience

      Volume: 24 Issue: 5 Pages: 102424-102424

    • DOI

      10.1016/j.isci.2021.102424

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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
    • Journal Title

      Scientific Reports

      Volume: - Issue: 1 Pages: 10439-10439

    • DOI

      10.1038/s41598-021-89836-7

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 30;525 Issue: 2 Pages: 477-482

    • DOI

      10.1016/j.bbrc.2020.02.101

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [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.
    • Journal Title

      British Journal of Cancer

      Volume: 122 Issue: 8 Pages: 1185-1193

    • DOI

      10.1038/s41416-020-0757-2

    • Related Report
      2019 Research-status 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

      10.1007/s12185-019-02595-0

    • Related Report
      2019 Research-status Report 2018 Research-status 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

      10.1016/j.jid.2019.01.029

    • Related Report
      2018 Research-status 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

      10.1111/cas.13958

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [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

      10.1093/intimm/dxz004

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 生体内における樹状細胞への腫瘍抗原送達システムによる新規がんペプチドワクチン療法2018

    • Author(s)
      水本有紀、勝田将裕、宮澤基樹、北畑裕司、宮本篤、中森幹人、尾島敏康、松田健司、邊見弘明、玉田耕治、改正恒康、山上裕機
    • Journal Title

      癌と化学療法

      Volume: 45 Pages: 1469-1471

    • Related Report
      2018 Research-status Report
  • [Presentation] 遺伝子改変マウスを用いた自己炎症性疾患病態解明へのアプローチ2020

    • Author(s)
      邊見弘明
    • Organizer
      愛媛大学プロテオサイエンスセンター(PROS)第8回学術シンポジウム難病のプロテオ医学研究2020 細胞死・炎症シグナル伝達機構の破綻による疾患と創薬2
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Impaired development of myeloid cells in mice carrying a patient-derived proteasome subunit mutation.2020

    • Author(s)
      邊見弘明、折茂貴是、佐々木泉、加藤喬、大田(福田)有里、金城紀子、浜田聡、木下晃、吉浦孝一郎、大西秀典、金澤伸雄、改正恒康
    • Organizer
      第3回日本免疫不全・自己炎症学会学術集会
    • Related Report
      2019 Research-status Report
  • [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
      2019 Research-status Report
    • Int'l Joint Research
  • [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
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Dermal dendritic cells present neo-self antigens induced by ultraviolet B exposure to expand Foxp3+ regulatory T cells.2019

    • Author(s)
      Sayuri Yamazaki, Mizuyu Odanaka, Hiroaki Shime, Masaki Imai, Hiroaki Hemmi, Tsuneyasu Kaisho, Naganari Ohkura, Shimon Sakaguchi, Akimichi Morita.
    • Organizer
      Society for Investigative Dermatology (SID) 77th Annual Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Analysis of mice carrying a novel and missense mutation of proteasome subunit gene identified in a patient with autoinflammation and immune deficiency.2019

    • Author(s)
      Hiroaki Hemmi, Takashi Orimo, Naoko Nishiyama, Takashi Kato, Toshiya Ozasa, Izumi Sasaki, Noriko Kinjo, Nobuo Kanazawa, Tsuneyasu Kaisho.
    • Organizer
      The 26th International Symposium on Molecular Cell Biology of Macrophages.
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Cholera toxin B can induce interleukine-1β production in peritoneal macrophages through the pyrin inflammasome as well as the NLRP3 inflammasome.2019

    • Author(s)
      Sasaki I, Orimo T, Hemmi H, Furukawa K, Kaisho T.
    • Organizer
      The 26th International Symposium on Molecular Cell Biology of Macrophages.
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] ヒト疾患由来プロテアソームサブユニット突然変異導入マウスにおける樹状細胞分化障害2019

    • Author(s)
      邊見弘明、小笹俊哉、加藤喬、折茂貴是、佐々木泉、大田(福田)有里、金澤伸雄、改正恒康.
    • Organizer
      第29回日本樹状細胞研究会
    • Related Report
      2019 Research-status Report
  • [Presentation] コレラ毒素Bサブユニットは細胞内病原体センサーNLRP3とPyrinを介して炎症性サイトカインIL-1βの産生を誘導する2019

    • Author(s)
      佐々木泉、折茂貴是、邊見弘明、古川鋼一、改正恒康
    • Organizer
      第29回日本樹状細胞研究会
    • Related Report
      2019 Research-status Report
  • [Presentation] コレラ毒素Bサブユニットによる炎症性サイトカインIL-1β産生誘導機構2019

    • Author(s)
      佐々木泉、折茂貴是、邊見弘明、土屋慧馬、井上正一、熊谷直光、古川鋼一、改正恒康
    • Organizer
      第26回日本免疫毒性学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Cholera toxin B can induce interleukine-1β production from resident per itoneal macrophages in synergy with lipopolysaccharides.2019

    • Author(s)
      Sasaki I, Orimo T, Hemmi H, Furukawa K, Kaisho T.
    • Organizer
      The 18th Awaji International Forum on Infection and Immunity
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Regulatory T cells with a distinctive feature expand through dermal dendritic cells in the ultraviolet B exposed skin.2019

    • Author(s)
      Sayuri Yamazaki, Mizuyu Odanaka, Hiroaki Shime, Masaki Imai, Hiroaki Hemmi, Tsuneyasu Kaisho, Naganari Ohkura, Shimon Sakaguchi, Akimichi Morita.
    • Organizer
      16th International Workshop on Langerhans Cells
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [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
      2019 Research-status Report
  • [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
      2019 Research-status Report
  • [Presentation] Roles of endoplasmic reticulum stress in cholera toxin B-induced interleukine-1β production from resident peritoneal macrophages.2019

    • Author(s)
      Sasaki I, Morita S, Okuzaki D, Orimo T, Hemmi H, Furukawa K, Kaisho T.
    • Organizer
      第48回日本免疫学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Successful treatment of psoriatic inflammation restores hyperglycemia2018

    • Author(s)
      Kyoko Ikumi, Mizuyu Odanaka, Hiroaki Shime, Masaki Imai, Osamu Taguchi, Hiroaki Hemmi, Tsuneyasu Kaisho, Sayuri Yamazaki, Akimichi Morita
    • Organizer
      International Investigative Dermatology 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 中條ー西村症候群からプロテアソーム関連自己炎症/免疫不全症候群へ2018

    • Author(s)
      金澤伸雄、中谷友美、原知之、稲葉豊、国本佳代、古川福実、神人正寿、金城紀子、水島恒裕、三嶋博之、木下晃、吉浦孝一郎、邊見弘明、改正恒康
    • Organizer
      第25回分子皮膚科学フォーラム
    • Related Report
      2018 Research-status Report
  • [Presentation] ケモカイン受容体XCR1陽性樹状細胞の機能的意義2018

    • Author(s)
      邊見弘明、改正恒康
    • Organizer
      第40回日本比較免疫学会
    • Related Report
      2018 Research-status Report
    • Invited
  • [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
      2018 Research-status Report
  • [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
      2018 Research-status Report
  • [Presentation] A case of neonatal-onset proteasome-associated autoinflammatory syndrome resembling but distinct from Nakajo-Nishimura syndrome2018

    • Author(s)
      Noriko Kinjo, Hiroyuki Mishima, Akira Kinoshita, Koh-Ichiro Yoshiura, Tsunehiro Mizushima, Jun Hamazaki, Shigeo Murata, Hiroaki Hemmi, Tsuneyasu Kaisho, Nobuo Kanazawa
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] A mouse model of LIG4 syndrome with novel LIG4 mutation2018

    • Author(s)
      Yusuke Yamashita, Shinobu Tamura, Yuri Fukuda, Toshiya Ozasa, Nobuo Kanazawa, Hiroaki Hemmi, Koichiro Yoshiura, Tsuneyasu Kaisho, Takashi Sonoki
    • Organizer
      第80回日本血液学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 生体内樹状細胞送達システムによる新規がんペプチドワクチン療法2018

    • Author(s)
      水本有紀、勝田将裕、宮澤基樹、北畑裕司、宮本篤、中森幹人、尾島敏康、松田健司、邊見弘明、玉田耕治、改正恒康、山上裕機
    • Organizer
      第39回癌免疫外科研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] 樹状細胞サブセットに注目したがんペプチドワクチン療法2018

    • Author(s)
      水本有紀、勝田将裕、宮澤基樹、北畑裕司、宮本篤、中森幹人、松田健司、尾島敏康、邊見弘明、玉田耕治、改正恒康、山上裕機
    • Organizer
      第77回日本癌学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 樹状細胞サブセットへの送達に注目したがんペプチドワクチン療法2018

    • Author(s)
      水本有紀、勝田将裕、邊見弘明、宮澤基樹、北畑裕司、宮本篤、小林良平 、中森幹人、尾島敏康、松田健司、中村公紀 早田啓治、玉田耕治、改正恒康、山上裕機
    • Organizer
      第31回日本バイオセラピィ学会学術集会総会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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