Elucidation of pathological regulation of tissue-resident memory CD4 T cells in lung fibosis

• Project/Area Number: 17K08876
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: Chiba University
• Principal Investigator: Hirahara Kiyoshi 千葉大学, 大学院医学研究院, 准教授 (00707193)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 真菌感染症 / アスペルギルス / 肺線維化 / CD4 / 組織局在性記憶 / CD103 / Foxp3 / RNA-Seq / CD4組織局在性記憶 / 肺繊維症 / 真菌感染 / 獲得免疫 / 組織局在記憶T細胞

Outline of Final Research Achievements

The study aims to elucidate the roles of CD4 tissue resident memory T (TRM) cells in the pathology of lung fibrosis by using our original mouse model of chronic airway inflammation by repeated exposure of fungal (Aspergillus) antigens. We identified two types of CD4 TRM cells induced by Aspergillus antigen. We found that CD103-negative TRM cells produced proinflammatory cytokines and induced fibrosis, whereas CD103-positive TRM cells were regulatory T cells that highly expressed Foxp3 and inhibited fibrosis.

Academic Significance and Societal Importance of the Research Achievements

本研究で対象にする難治性呼吸器疾患である肺線維症は、いまだに対処療法しかなく生命予後も非常に悪い。本研究計画は、Human Immunologyを視点においた研究であり、呼吸器内科医としての臨床経験と基礎研究医の両方の背景を有する申請者の強みを活かしている。肺線維症は加齢とともに発症率が高くなる。またCOVID-19などによる重症肺炎でも肺線維化が起こる。本申請研究で線維症患者のTRM CD4 T細胞の分子基盤を構築することで、現在根治治療法が全くない肺線維症に対する新たな治療戦略提示のための分子基盤を構築することが可能となり、その社会的・経済的インパクトは計り知れない。

Research Products

• [Journal Article] Histone deacetylase 1 (HDAC1): A key player of T cell-mediated arthritis (2020)
  • Author(s): Goschl,L, Preglej,T, Boucheron,N, Saferding,V, Muller,L, Platzer,A, Hirahara,K, Han-Yu,S, Backlund,J, Matthias,P, Niederreiter,B, Hladik,A, Kugler,M, Gualdoni,G, Scheinecker,C, Knapp,S, Seiser,C, Holmdahl,R, Tillmann,K, Plasenzotti,R, Podesser,B, Aletaha,D, Smolen, Karonitsch,TJ, Steiner,G, Ellmeier,W, Bonelli,M
  • Journal Title: Journal of Autoimmunity Volume: 108 Pages: 102379-102379
  • DOI: 10.1016/j.jaut.2019.102379
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] CD103hi Treg cells constrain lung fibrosis induced by CD103lo tissue-resident pathogenic CD4 T cells (2019)
  • Author(s): Ichikawa, T.*, Hirahara, K.*, Kokubo, K.*, Kiuchi, M., Aoki, A., Morimoto, Y., Kumagai, J., Onodera, A., Mato, N., Tumes, D., Goto, Y., Hagiwara, K., Inagaki, Y., Sparwasser, T., Tobe, K., and Nakayama, T.
  • Journal Title: Nature Immunology Volume: 20 Issue: 11 Pages: 1469-1480
  • DOI: 10.1038/s41590-019-0494-y
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Pathogenicity of acquired immunity in human diseases (2019)
  • Author(s): Hirahara, K
  • Journal Title: Seminars in Immunopathology Volume: 41 Issue: 3 Pages: 279-281
  • DOI: 10.1007/s00281-019-00739-2
  • Peer Reviewed / Open Access
• [Journal Article] The immunopathology of lung fibrosis: amphiregulin-producing pathogenic memory T helper-2 cells control the airway fibrotic responses by inducing eosinophils to secrete osteopontin. (2019)
  • Author(s): Hirahara, K, Aoki, A, Morimoto, Y, Kiuchi, M, Okano, M, Nakayama, T
  • Journal Title: Semin. Immunopathol. Volume: 41(3) Issue: 3 Pages: 339-348
  • DOI: 10.1007/s00281-019-00735-6
  • Peer Reviewed / Open Access
• [Journal Article] 各種サイトカインで誘導される2型免疫応答による組織線維化のしくみ (2019)
  • Author(s): 平原潔, 中山俊憲
  • Journal Title: 医学のあゆみ Volume: 271(5) Pages: 486-490
• [Journal Article] 【新時代が始まった-アレルギー疾患研究 疾患多様性を理解し病態の層別化に基づく治療を実現する】(第1章)アレルギーのメカニズム研究 免疫細胞とサイトカインなど アレルギー性気道炎症の病態形成におけるPathogenic Th2細胞の多様な役割 (2019)
  • Author(s): 青木 亜美, 平原 潔, 中山 俊憲
  • Journal Title: 実験医学 Volume: 37(10) Pages: 1561-1566
• [Journal Article] アレルギ－性気道炎症の病態形成におけるPathogenic Th2細胞の多様な役割 (2019)
  • Author(s): 青木亜美, 平原潔, 中山俊憲
  • Journal Title: 実験医学 増刊 Volume: 37(10) Pages: 49-54
• [Journal Article] 専門医のためのアレルギー学講座 免疫学における基礎と新たな展開 病原性Th細胞 (2019)
  • Author(s): 森本 侑樹, 平原 潔, 中山 俊憲
  • Journal Title: アレルギー Volume: 68(3) Pages: 138-143
• [Journal Article] An Optimized protocol for the analysis of House dust mites (Dermatophagoides farinae) induced neutrophil-dominant airway inflammation with fibrosis (2019)
  • Author(s): Wada, T., Hirahara, K., Aoki, A., Morimoto, Y., Kiuchi, M., Kumagai, J., Okano, M., Kokubo, K., Kato, M., Fukano, C., Ohashi-Doi, K., and Nakayama, T.
  • Journal Title: J. Immunol. Methods Volume: 465 Pages: 53-60
  • DOI: 10.1016/j.jim.2018.12.003
  • Peer Reviewed
• [Journal Article] Ezh2 controls development of natural killer T cells, which cause spontaneous asthma-like pathology (2019)
  • Author(s): Tumes, D., Hirahara, K., Papadopoulos, M., Shinoda, K., Onodera, A., Kumagai, J., Yip, KH., Pant, H., Kokubo, K., Masahiro, K., Aoki, A., Obata-Ninomiya, K., Yokoyoda, K., Endo, Y., Kimura, MY., Nakayama, T.
  • Journal Title: Journal of Allergy and Clinical Immunology Volume: 0091-6749(19) Issue: 2 Pages: 30340-9
  • DOI: 10.1016/j.jaci.2019.02.024
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Immune cell-epithelial/mesenchymal interaction contributing to allergic airway inflammation associated pathology (2019)
  • Author(s): Hirahara, K., Shinoda, K., Morimoto, Y., Kiuchi, M., Aoki, A., Kumagai, J., Kokubo, K., and Nakayama, T.
  • Journal Title: Front. Immunol Volume: -
  • Peer Reviewed
• [Journal Article] Pathogenicity of Acquired Immunity in Human Diseases (2019)
  • Author(s): Hirahara, K.
  • Journal Title: Semin. Immunopathol. Volume: -
  • Peer Reviewed
• [Journal Article] The immunopathology of lung fibrosis: Amphiregulin-producing pathogenic memory T helper-2 cells control the airway fibrotic responses by inducing eosinophils to secrete osteopntin (2019)
  • Author(s): Hirahara, K., Aoki, A., Morimoto, Y., Kiuchi, M., Okano, M., and Nakayama, T.
  • Journal Title: Semin. Immunopathol. Volume: -
  • Peer Reviewed
• [Journal Article] Amphiregulin-Producing Pathogenic Memory T Helper 2 Cells Instruct Eosinophils to Secrete Osteopontin and Facilitate Airway Fibrosis (2018)
  • Author(s): Morimoto, Y., Hirahara, K., Kiuchi, M., Wada, T., Ichikawa, T., Kanno, T., Okano, M., Kokubo, K., Onodera, A., Sakurai, D., Okamoto, Y., Nakayama, T.
  • Journal Title: Immunity Volume: 49 Issue: 1 Pages: 134-150
  • DOI: 10.1016/j.immuni.2018.04.023
  • Peer Reviewed
• [Journal Article] CXCR6+ST2+ memory T helper 2 cells induced the expression of major basic protein in eosinophils to reduce the fecundity of helminth (2018)
  • Author(s): Obata-Ninomiya, K., Ishiwata, K., Nakano, H., Endo, Y., Ichikawa, T., Onodera, A., Hirahara, K., Okamoto, Y., Kanuka, H., Nakayama, T.
  • Journal Title: Proceedings of the National Academy of Sciences Volume: 115 Issue: 42
  • DOI: 10.1073/pnas.1714731115
  • Peer Reviewed / Open Access
• [Journal Article] DUSP10 constrains innate IL-33-mediated cytokine production in ST2hi memory-type pathogenic Th2 cells (2018)
  • Author(s): Yamamoto, T., Endo, Y., Onodera, A., Hirahara, K., Asou, H., Nakajima, T., Kanno, T., Ouchi, Y., Uematsu, S., Nishimasu, H., Nureki, O., Tumes, D. J., Shimojo, N., and Nakayama, T.
  • Journal Title: Nature Communications Volume: 9 Issue: 1 Pages: 4231-4231
  • DOI: 10.1038/s41467-018-06468-8
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Maintenance of memory-type pathogenic Th2 cells in the pathophysiology of chronic airway inflammation (2018)
  • Author(s): Hirahara K, Shinoda K, Endo Y, Ichikawa T, Nakayama T.
  • Journal Title: Inflammation and Regeneration 2018 Volume: 印刷中
  • Peer Reviewed
• [Journal Article] The pathogenicity of IL-33 on steroid-resistant eosinophilic inflammation via the activation of memory-type ST2+CD4+ T cells (2018)
  • Author(s): Hirahara K, Mato N, Hagiwara K, Nakayama T.
  • Journal Title: J Leukoc Biol. Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Pathogenicity of memory Th2 cells is linked to stage of allergic rhinitis (2018)
  • Author(s): Iinuma T.、Okamoto Y.、Morimoto Y.、Arai T.、Sakurai T.、Yonekura S.、Sakurai D.、Hirahara K.、Nakayama T.
  • Journal Title: Allergy Volume: 73 Issue: 2 Pages: 479-489
  • DOI: 10.1111/all.13295
  • Peer Reviewed / Open Access
• [Journal Article] A T cell-specific deletion of HDAC1 protects against experimental autoimmune encephalomyelitis (2018)
  • Author(s): Goschl L, Preglej T, Hamminger P, Bonelli M, Andersen L, Boucherron N, Gulich A, Muller L, Saferding V, Mufazolov AI, Hirahara K, Seiser C, Matthias P, Penz T, Schuster M, Bock C, Waisman A, Steiner G, Ellmeier W.
  • Journal Title: J Autoimmun Volume: 86 Pages: 51-61
  • DOI: 10.1016/j.jaut.2017.09.008
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Anti-tumor immunity via the superoxide-eosinophil axis induced by a lipophilic component of Mycobacterium lipomannan (2017)
  • Author(s): Ito Toshihiro、Hirahara Kiyoshi、Onodera Atsushi、Koyama-Nasu Ryo、Yano Ikuya、Nakayama Toshinori
  • Journal Title: Int. Immunol Volume: 29 Issue: 9 Pages: 411-421
  • DOI: 10.1093/intimm/dxx051
  • Peer Reviewed / Open Access
• [Journal Article] Menin Controls the Memory Th2 Cell Function by Maintaining the Epigenetic Integrity of Th2 Cells (2017)
  • Author(s): Onodera Atsushi、Kiuchi Masahiro、Kokubo Kota、Kato Miki、Ogino Tomohiro、Horiuchi Shu、Kanai Urara、Hirahara Kiyoshi、Nakayama Toshinori
  • Journal Title: J Immunol Volume: 199 Issue: 3 Pages: 1153-1162
  • DOI: 10.4049/jimmunol.1602129
  • Peer Reviewed / Open Access
• [Journal Article] Memory-type ST2+CD4+ T cells participate in the steroid-resistant pathology of eosinophilic pneumonia (2017)
  • Author(s): Mato Naoko、Hirahara Kiyoshi、Ichikawa Tomomi、Kumagai Jin、Nakayama Masayuki、Yamasawa Hideaki、Bando Masashi、Hagiwara Koichi、Sugiyama Yukihiko、Nakayama Toshinori
  • Journal Title: Sci Rep Volume: 7 Issue: 1 Pages: 6805-6805
  • DOI: 10.1038/s41598-017-06962-x
  • Peer Reviewed / Open Access
• [Journal Article] The Transcription Factor T-bet Limits Amplification of Type I IFN Transcriptome and Circuitry in T Helper 1 Cells (2017)
  • Author(s): Iwata Shigeru、Mikami Yohei、Sun Hong-Wei、Brooks Stephen R.、Jankovic Dragana、Hirahara Kiyoshi、Onodera Atsushi、Shih Han-Yu、Kawabe Takeshi、Jiang Kan、Nakayama Toshinori、Sher Alan、O’Shea John J.、Davis Fred P.、Kanno Yuka
  • Journal Title: Immunity Volume: 46 Issue: 6 Pages: 983-991.e4
  • DOI: 10.1016/j.immuni.2017.05.005
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Epigenetic regulation of T-helper cell differentiation, memory, and plasticity in allergic asthma (2017)
  • Author(s): Tumes Damon J.、Papadopoulos Magdalene、Endo Yusuke、Onodera Atsushi、Hirahara Kiyoshi、Nakayama Toshinori
  • Journal Title: Immunol. Rev Volume: 278 Issue: 1 Pages: 8-19
  • DOI: 10.1111/imr.12560
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Maintenance of pathogenic Th2 cells in allergic disorders (2017)
  • Author(s): Shinoda K, Hirahara K, Nakayama T.
  • Journal Title: Allergology International Volume: 66 Issue: 3 Pages: 369-376
  • DOI: 10.1016/j.alit.2017.03.005
  • NAID: 130005858825
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Open Access
• [Journal Article] Th2 cells in health and disease. (2016)
  • Author(s): Nakayama T, Hirahara K, Onodera A, Endo Y, Hosokawa H, Shinoda K, Tumes DJ, Okamoto Y.
  • Journal Title: Annu Rev Immunol. Volume: 35 Issue: 1 Pages: 53-84
  • DOI: 10.1146/annurev-immunol-051116-052350
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] アレルギー炎症に伴う線維化に対する新規治療法開発 (2020)
  • Author(s): 平原潔、小野寺淳、飯沼智久、間藤尚子
  • Organizer: 難治性疾患実用化研究事業 免疫アレルギー疾患実用化研究事業 2019年度合同成果報告会
• [Presentation] CD103hi Treg cells regulate lung fibrotic response induced by CD103lo tissue-resident pathogenic CD4 T cells. (2019)
  • Author(s): Hirahara, K
  • Organizer: 2019 NIH-Japan-JSPS symposium
  • Int'l Joint Research
• [Presentation] CD103hi Treg cells regulate lung fibrotic response induced by CD103lo tissue-resident pathogenic CD4 T cells. (2019)
  • Author(s): Hirahara, K, Ichikawa, T, Kokubo, K, Kiuchi, M, Aoki, A, Morimoto, Y, Kumagai, J, Nakayama, T
  • Organizer: The 7th Annual Meeting of the International Cytokine and Interferon Society
  • Int'l Joint Research
• [Presentation] 肺の線維化を誘導する新たな「細胞-分子機構」 (2019)
  • Author(s): 平原潔
  • Organizer: Scientific Exchange Meeting in Osaka
• [Presentation] Cellular and molecular mechanisms underlying the induction of fibrotic responses in the lung. (2019)
  • Author(s): Hirahara, K
  • Organizer: The 1st Chiba University-University Toronto Workshop
  • Int'l Joint Research
• [Presentation] Amphiregulin-producing pathogenic memory T helper-2 cells drive airway fibrosis via activation of eosinophils. (2019)
  • Author(s): Hirahara, K, Morimoto, Y, Kiuchi, M, Okano, M, Kokubo, K, Nakayama, T
  • Organizer: Tissue Repair and Regeneration (Gordon Research Conference)
  • Int'l Joint Research
• [Presentation] 好酸球性気道炎症において線維化誘導-病原性ヘルパーT細胞が誘導する組織線維化の形成機構について (2019)
  • Author(s): 平原潔
  • Organizer: 第12回次世代アジュバント研究会
• [Presentation] 好酸球性アレルギー炎症において組織線維化を引き起こす線維化誘導-病原性ヘルパーT細胞を標的とした新規線維化治療法開発 (2019)
  • Author(s): 平原潔、小野寺淳、森本侑樹、間藤尚子
  • Organizer: 東京国際フォーラム, 東京（ポスター発表）
• [Presentation] Tissue remodeling fibrosis in mucosal sites of the airway (2019)
  • Author(s): Hirahara, K.
  • Organizer: The 3nd Chiba University-UC San Diego Symposium “Mucosal Immunology, Allergy and Vaccine”
  • Int'l Joint Research
• [Presentation] 病原性Th2細胞による喘息の発症と炎症遷延化の最新知見 (2019)
  • Author(s): 平原潔
  • Organizer: Scientific Exchange Meeting in 栃木 ～アレルギー週間 2019～
• [Presentation] 病原性ヘルパー細胞による慢性アレルギー性気道炎症の病態形成機構 (2019)
  • Author(s): 平原潔
  • Organizer: 第3回アレルギー治療updateフォーラム
• [Presentation] 好酸球性気道炎症において線維化誘導-病原性ヘルパーT細胞が誘導する組織線維化の形成機構について (2018)
  • Author(s): 平原潔、森本侑樹、木内政宏、和田朋子、市川智巳、岡野美樹子、小野寺淳、櫻井大樹、岡本美孝、中山俊憲
  • Organizer: 第67回日本アレルギー学会,シンポジウム 16
  • Invited
• [Presentation] Amphiregulin-producing pathogenic memory T helper-2 cells drive airway fibrosis via activation of eosinophils (2018)
  • Author(s): Hirahara, K., Morimoto, Y., Kiuchi, M., Okano, M., Kokubo, K., Onodera, A., Sakurai, D., Okamoto, Y., Nakayama, T.
  • Organizer: The 6th Annual Meeting of the International Cytokine and Interferon Society (ICIS 2018)
  • Int'l Joint Research
• [Presentation] 線維化誘導-病原性ヘルパーT細胞が誘導する組織線維化の形成機構について (2018)
  • Author(s): 平原潔、森本侑樹、木内政宏、和田朋子、市川智巳、岡野美樹子、小野寺淳、櫻井大樹、岡本美孝、中山俊憲
  • Organizer: 第46回日本臨床免疫学会,ワークショップ 6
  • Invited
• [Presentation] Pathogenic Th population disease induction model: From the recruitment of eosinophils to the induction of fibrosis (2018)
  • Author(s): Hirahara, K., Morimoto, Y., Kiuchi, M., Okano, M., Kokubo, K., Ogino, T., and Nakayama, T.
  • Organizer: 第47回日本免疫学会総会・学術集会
• [Presentation] Orally-desensitized mast cells acquired regulatory characteristics for the control of food allergy (2018)
  • Author(s): Kurashima, Y., Takasato, Y., Kiuchi, M., Hirahara, K., Murasaki, S., Kunisawa, J., Kubo, M., Uematsu, S., Nakayama, T., and Kiyono, H.
  • Organizer: 第47回日本免疫学会総会・学術集会
• [Presentation] 気道粘膜免疫とアレルギー (2018)
  • Author(s): 平原潔
  • Organizer: 第5回総合アレルギ－講習会～Total Allergistをめざして～
• [Presentation] 線維化誘導-病原性ヘルパーT細胞によるイムノエイジング病態形成機構の解析と病態制御 (2018)
  • Author(s): 平原潔
  • Organizer: 老化メカニズムの解明・制御プロジェクト、AMED-CREST/PRIME「機能低下」合同リトリート会議
• [Presentation] 病原性ヘルパーT細胞による慢性アレルギー性炎症の病態形成機構 (2018)
  • Author(s): 平原潔
  • Organizer: 第17回 お茶の水眼アレルギー研究会
• [Presentation] Pathogenic Th population disease induction model: From the recruitment of eosinophils to the induction of fibrosis (2018)
  • Author(s): Hirahara K
  • Organizer: The 2nd Chiba University-UC San Diego Symposium “Mucosal Immunology, Allergy and Vaccine”
  • Int'l Joint Research / Invited
• [Presentation] Memory-type CD62LlowCD44hi ST2+CD4+ T cells contribute to the steroid-resistant pathology of eosinophilic pneumonia (2018)
  • Author(s): Hirahara K, Mato N, Ichikawa T, Kumagai J, Nakayama M, Yamasawa H, Bando M, Hagiwara K, Sugiyama Y, Nakayama T
  • Organizer: Keystone Symposia Immunological Memory (X1)
  • Int'l Joint Research
• [Presentation] 記憶型ヘルパーT細胞の多様性・可塑性: -慢性気道炎症における記憶型病原性Th2(Tpath2)細胞の役割- (2017)
  • Author(s): 平原潔, 小野寺淳, 森本侑樹, 間藤尚子
  • Organizer: Legend Seminar 2017
  • Invited
• [Presentation] 免疫記憶の最新知見: -記憶型T細胞の研究最前線 (2017)
  • Author(s): 平原潔, 小野寺淳, 森本侑樹, 間藤尚子
  • Organizer: Legend Seminar 2017
  • Invited
• [Presentation] Memory-type ST2+CD4+ T cells participate in the steroid-resistant pathology of eosinophilic pneumonia (2017)
  • Author(s): Hirahara K, Mato N, Ichikawa T, Kumagai J, Nakayama M, Yamasawa H, Bando M, Hagiwara K, Sugiyama Y, Nakayama T.
  • Organizer: The 5th Annual Meeting of the International Cytokine and Interferon Society
  • Int'l Joint Research
• [Presentation] 肺バリア障害における記憶型病原性Th2(Tpath2)細胞の役割 (2017)
  • Author(s): 平原潔、中山俊憲
  • Organizer: 第66回日本アレルギー学会
  • Invited
• [Book] Induction and regulation of mucosal memory T cell response (2020)
  • Author(s): Hirahara, K, Nakayama, T
  • Total Pages: 940
  • Publisher: MUCOSAL VACCINES Second Edition ELSEVIER
  • ISBN: 9780128119242
• [Remarks] 千葉大学大学院医学研究院免疫発生学
  • URL: https://www.m.chiba-u.ac.jp/class/meneki/jisseki/index.html
• [Remarks] 千葉大学大学院 医学研究院 免疫発生学
  • URL: https://www.m.chiba-u.ac.jp/class/meneki/
• [Remarks] 千葉大学大学院医学研究院免疫発生学
  • URL: http://www.m.chiba-u.ac.jp/class/meneki/
• [Patent(Industrial Property Rights)] IL-33関連疾患の予防又は治療剤 (2019)
  • Inventor(s): 中山俊憲, 熊谷仁, 平原潔, 木内政宏
  • Industrial Property Rights Holder: 国立大学法人千葉大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2019-057333
  • Filing Date: 2019
• [Patent(Industrial Property Rights)] 細胞外基質の産生抑制剤及びその使用 (2018)
  • Inventor(s): 森本侑樹、中山俊憲、岡本美孝、平原潔
  • Industrial Property Rights Holder: 国立大学法人 千葉大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2018
• [Patent(Industrial Property Rights)] 細胞外基質の産生抑制剤及びその使用 (2017)
  • Inventor(s): 森本侑樹、中山俊憲、岡本美孝、平原潔
  • Industrial Property Rights Holder: 千葉大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2017-176017
  • Filing Date: 2017