炎症性組織レジリエンスと組織障害エントロピーの統合的理解と炎症収束学の創成

2023 Fiscal Year Annual Research Report

• Project Area: Integrated elucidation of inflammatory tissue-resilience and tissue damage-entropy;Creation of innovative science for resolution of inflammation
• Project/Area Number: 21H05120
• Research Institution: Chiba University
• Principal Investigator: 平原 潔 千葉大学, 大学院医学研究院, 教授 (00707193)
• Co-Investigator(Kenkyū-buntansha): 新井 郷子 一般社団法人AIM医学研究所, 研究部門, 副所長 (60422276) ; 三上 洋平 慶應義塾大学, 医学部(信濃町), 准教授 (80528662)
• Project Period (FY): 2021-08-23 – 2024-03-31
• Keywords: 炎症収束 / 炎症記憶 / 炎症性組織レンジエンス / 組織障害エントロピー

Outline of Annual Research Achievements

本領域では、「炎症収束」をキーワードに様々なバックグランドを持つ異分野領域を専門とする研究者が結集している。この研究者が一丸となって、研究を推進し、目標を達成するため、総括班により、研究者間の有機的連携を強化している。そのため、研究支援システムを整備し（研究支援担当）、ホームページを充実させ（広報担当）、定期的に領域会議、シンポジウムを開催してきた（集会担当）。また、総括班のリーダーシップのもと、計画班員間の有機的研究連携体制を確立し、「炎症収束学」創成にむけた研究を推進する。それぞれが有機的な連携を図りながら、領域全体で一丸となり、炎症収束時の組織の制御、調和、記憶を司る「炎症性組織レジリエンス」機構の統合的な理解を目指している。
総括班の研究代表者を平原が務め、各計画研究代表者が総括班の研究分担者として、研究支援システムの整備（平原：研究班内での研究の有機的連携を行うための解析支援整備）、領域会議・国際シンポジウムの開催（新井：年1回の領域会議開催による研究成果の共有と研究班員間の共同研究に向けた有機的連携形成、第３回炎症収束研究会（2024年2月14日-15日、熱海））((The International Symposium on Resolution of Inflammation（2024年1月18日、千葉))、成果の発信（三上：ホームページの開設による研究成果の情報発信,https://www.ensho-shusoku.jp/)）をそれぞれが行っている。なお、炎症領域に関わる先端的研究を行っている鍋島陽一先生（神戸医療産業都市推進機構先端医療研究センター）、河上裕先生（国際医療福祉大学医学部）、岩間厚志先生（東京大学医科学研究所）が研究協力者として、領域全体の評価および助言を頂いている。

Research Progress Status

令和5年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和5年度が最終年度であるため、記入しない。

Research Products

• [Int'l Joint Research] シャリテー医科大学(ドイツ)
  • Country Name: GERMANY
  • Counterpart Institution: シャリテー医科大学
• [Journal Article] 腎疾患におけるAIMの関与 (2024)
  • Author(s): 新井響子,宮崎徹
  • Journal Title: アニムス Volume: 118 Pages: 34-38
• [Journal Article] The USP7-STAT3-granzyme-Par-1 axis regulates allergic inflammation by promoting differentiation of IL-5-producing Th2 cells (2023)
  • Author(s): Kumagai Jin、Kiuchi Masahiro、Kokubo Kota、Yagyu Hiroyuki、Nemoto Masahiro、Tsuji Kaori、Nagahata Ken、Sasaki Atsushi、Hishiya Takahisa、Onoue Miki、Shinmi Rie、Sonobe Yuri、Iinuma Tomohisa、Yonekura Syuji、Shinga Jun、Hanazawa Toyoyuki、Koseki Haruhiko、Nakayama Toshinori、Yokote Koutaro、Hirahara Kiyoshi
  • Journal Title: Proceedings of the National Academy of Sciences Volume: 120(49) Pages: 2302903120
  • DOI: 10.1073/pnas.2302903120
  • Peer Reviewed / Open Access
• [Journal Article] Single-cell RNA sequencing of peripheral blood mononuclear cells from Kimura disease patient successfully treated with dupilumab (2023)
  • Author(s): Suga Kensuke、Kiuchi Masahiro、Kageyama Takahiro、Kokubo Kota、Tanaka Shigeru、Iwata Arifumi、Suzuki Kotaro、Hirahara Kiyoshi、Nakajima Hiroshi
  • Journal Title: Allergology International Volume: 72(4) Pages: 610～613
  • DOI: 10.1016/j.alit.2023.06.002
  • Peer Reviewed / Open Access
• [Journal Article] Differences in the expression of multidrug resistance proteins in chronic rhinosinusitis according to endotype (2023)
  • Author(s): Iinuma Tomohisa、Yonekura Syuji、Hirahara Kiyoshi、Kurita Junya、Yoneda Riyo、Arai Tomoyuki、Sonobe Yuri、Shinmi Rie、Okamoto Yoshitaka、Hanazawa Toyoyuki
  • Journal Title: Allergology International Volume: 72(4) Pages: 564～5472
  • DOI: 10.1016/j.alit.2023.03.008
  • Peer Reviewed / Open Access
• [Journal Article] Pathogenic helper T cells as the novel therapeutic targets for immune-mediated intractable diseases (2023)
  • Author(s): Onodera Atsushi、Kokubo Kota、Okano Mikiko、Onoue Miki、Kiuchi Masahiro、Iwamura Chiaki、Iinuma Tomohisa、Kimura Motoko Y.、Ebihara Nobuyuki、Hanazawa Toyoyuki、Nakayama Toshinori、Hirahara Kiyoshi
  • Journal Title: Pharmacology Therapeutics Volume: 247 Pages: 108445
  • DOI: 10.1016/j.pharmthera.2023.108445
  • Peer Reviewed / Open Access
• [Journal Article] The roles of tertiary lymphoid structures in chronic diseases (2023)
  • Author(s): Sato Yuki、Silina Karina、van den Broek Maries、Hirahara Kiyoshi、Yanagita Motoko
  • Journal Title: Nature Reviews Nephrology Volume: 19 Pages: 525～537
  • DOI: 10.1038/s41581-023-00706-z
  • Peer Reviewed / Open Access
• [Journal Article] Apoptosis inhibitor of macrophages/CD5L enhances phagocytosis in the trabecular meshwork cells and regulates ocular hypertension (2023)
  • Author(s): Nemoto Hotaka、Honjo Megumi、Arai Satoko、Miyazaki Toru、Aihara Makoto
  • Journal Title: Journal of Cellular Physiology Volume: 238 Pages: 2451～2467
  • DOI: 10.1002/jcp.31097
  • Peer Reviewed / Open Access
• [Journal Article] AIM/CD5L ameliorates autoimmune arthritis by promoting removal of inflammatory DAMPs at the lesions (2023)
  • Author(s): Yasuda Keisuke、Shimodan Shieri、Maehara Natsumi、Hirota Aika、Iijima Ruka、Nishijima Akemi、Mori Haruka、Toyama Ran、Ito Atsumi、Yoshikawa Yuri、Arai Satoko、Miyazaki Toru
  • Journal Title: Journal of Autoimmunity Volume: 142 Pages: 103149
  • DOI: 10.1016/j.jaut.2023.103149
  • Peer Reviewed / Open Access
• [Journal Article] Divergent roles for STAT4 in shaping differentiation of cytotoxic ILC1 and NK cells during gut inflammation (2023)
  • Author(s): Scarno G, Mazej J, Laffranchi M, Di Censo C, Mattiola I, Candelotti AM, Pietropaolo G, Stabile H, Fionda C, Peruzzi G, Brooks SR, Tsai WL, Mikami Y, Bernardini G, Gismondi A, et al
  • Journal Title: Proceedings of the National Academy of Sciences Volume: 120(40) Pages: e2306761120
  • DOI: 10.1073/pnas.2306761120
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] “神経-免疫連関”と慢性炎症の病態形成 - 病原性CD4+ T (pathogenic T: Tpath)細胞による病的な痒みの誘導機構 (2024)
  • Author(s): 平原潔
  • Organizer: シンポジウム 第101回日本生理学会大会
  • Invited
• [Presentation] 「組織炎症記憶」の蓄積がもたらす慢性炎症の難治化とその制御」 (2024)
  • Author(s): 平原潔
  • Organizer: 第2回STROMA (Stromal cell neTwork in chROnic inflamMAtion and disease)
  • Invited
• [Presentation] 慢性炎症下における病原性記憶T細胞を起点とした難治性病態形成の分子・細胞機構 (2024)
  • Author(s): 平原潔
  • Organizer: 第48回皮膚科免疫セミナー
  • Invited
• [Presentation] Pathological tissue inflammatory memories shape the intractable pathology of chronic lung inflammation (2024)
  • Author(s): Hirahara, K
  • Organizer: 10th Global Network Forum on Infection and Immunity
  • Invited
• [Presentation] Development of next-generation mucosal vaccines by controlling “pathogenic” immune memory (2024)
  • Author(s): Hirahara, K
  • Organizer: (Lecture) Dr. Toshinori Nakayama Memorial cMAV-cSIMVa Workshop
  • Invited
• [Presentation] A novel subpopulation of fibroblasts involved in the formation of inducible bronchus-associated lymphoid tissue (iBALT) (2024)
  • Author(s): Hishiya, T., Kiuchi, M., Nakayama, T., Ohotori, S., and Hirahara, K
  • Organizer: Dr. Toshinori Nakayama Memorial cMAV-cSIMVa Workshop
• [Presentation] Physiological acid exposure in the esophagus activates esophageal immune system (2024)
  • Author(s): Kurosugi, A., Iwamura, C., Kaneko, T., and Hirahara, K
  • Organizer: Dr. Toshinori Nakayama Memorial cMAV-cSIMVa Workshop
• [Presentation] The effect of tissue hypoxia on the immune system in chronic inflammation (2024)
  • Author(s): Sasaki, A., Kiuchi, M., Yagyu, H., Suzuki, T., Nakayama, T., and Hirahara, K
  • Organizer: Dr. Toshinori Nakayama Memorial cMAV-cSIMVa Workshop
• [Presentation] Repetitive exposure to aspergillus antigen induces type 17 inflammation accompanied by alveolar epithelial cell differentiation (2024)
  • Author(s): Tsuji, K., Aoki, A., Kiuchi, M., Nemoto, M., Nakayama, T., and Hirahara, K
  • Organizer: Dr. Toshinori Nakayama Memorial cMAV-cSIMVa Workshop
• [Presentation] Diverse characteristics of pulmonary neuroendocrine cells reversed in chronic airway inflammation (2024)
  • Author(s): Nemoto, M., Kiuchi, M., Tsuji, K., Nakayama, T., and Hirahara, K
  • Organizer: Dr. Toshinori Nakayama Memorial cMAV-cSIMVa Workshop
• [Presentation] Lipolysis-microlipophagy cascade regulated by adipose triglyceride lipase drives pathogenic type 2 adaptive immunity via the PPARg-ST2 axis (2024)
  • Author(s): Yagyu, H., Kiuchi, M., Kokubo, K., Sasaki, A., Onodera, A., Iwamura, C., Kaneko, T., Nakayama, T., and Hirahara, K
  • Organizer: Dr. Toshinori Nakayama Memorial cMAV-cSIMVa Workshop
• [Presentation] The USP7-STAT3-granzyme-Par-1 axis regulates allergic inflammation by promoting differentiation of IL-5-producing Th2 cells (2024)
  • Author(s): Kumagai,J., Kiuchi, M., Kokubo, K., Yagyu, H., Nemoto, M., Tsuji. K., Nagahata, K., Sasaki, A., Hishiya, T., Onoue, M., Shinmi, R., Sonobe, Y., Iinuma, T., Yonekura, S., Shinga, J., Hanazawa, T., Koseki, H., Nakayama, T., Yokote, K., and Hirahara, K
  • Organizer: Dr. Toshinori Nakayama Memorial cMAV-cSIMVa Workshop
• [Presentation] Inflammation driven fibrosis and tissue repair (2024)
  • Author(s): Hirahara, K
  • Organizer: (Overview talk) The 52nd Annual Meeting of The Japanese Society for Immunology
  • Int'l Joint Research / Invited
• [Presentation] Memory-type pathogenic Th2 (Tpath2) cells in airway inflammation (2024)
  • Author(s): Hirahara, K., and Nakayama, T
  • Organizer: (Symposium) The 52nd Annual Meeting of The Japanese Society for Immunology
  • Int'l Joint Research / Invited
• [Presentation] Inflamed tissue-derived unsaturated fatty acids induce memory-type pathogenic Th2 cells via the PPARg-ST2 axis (2024)
  • Author(s): Yagyu, H., Kiuchi, M., Kokubo, K., Sasaki, A., Kaneko, T., Nakayama, T., and Hirahara, K
  • Organizer: The 52nd Annual Meeting of The Japanese Society for Immunology
  • Int'l Joint Research
• [Presentation] A novel subpopulation of fibroblasts involved in the formation of induciblebronchus-associated lymphoid tissue (iBALT) (2024)
  • Author(s): Hishiya, T., Kiuchi, M., Nakayama, T., and Hirahara, K
  • Organizer: The 52nd Annual Meeting of The Japanese Society for Immunology
  • Int'l Joint Research
• [Presentation] Thioredoxin-interacting protein is essential for memory T cell formation via the regulation of the redox metabolism (2024)
  • Author(s): Kokubo, K., Hirahara, K., Kiuchi, M., Tsuji, K., Sonobe, Y., Shinmi, R., Hishiya, T., Iwamura, C., Onodera, A., and Nakayama, T
  • Organizer: The 52nd Annual Meeting of The Japanese Society for Immunology
  • Int'l Joint Research
• [Presentation] Diverse characteristics of pulmonary neuroendocrine cells revealed in chronic airway inflammation (2024)
  • Author(s): Nemoto, M., Kiuchi, M., Tsuji, K., Nakayama, T., and Hirahara, K
  • Organizer: The 52nd Annual Meeting of The Japanese Society for Immunology
  • Int'l Joint Research
• [Presentation] The USP7-STAT3-granzyme-Par-1 axis regulates allergic inflammation by promoting differentiation of IL-5-producing Th2 cells (2024)
  • Author(s): Kiuchi, M., Kokubo, K., Yagyu, H., Nemoto, M., Tsuji, K., Hishiya, T., Onoue, M., Shinmi, R., Sonobe, Y., Nakayama, T., and Hirahara, K
  • Organizer: The 52nd Annual Meeting of The Japanese Society for Immunology
  • Int'l Joint Research
• [Presentation] Characterization of eosinophils and natural killer cells in nasal polyps and peripheral blood in eosinophilic chronic rhinosinusitis patients (2024)
  • Author(s): Tsuji, K., Aoki, A., Onodera, A., Kiuchi, M., Kokubo, K., Morimoto, Y., Iinuma, T., Hanazawa, T., Nakayama, T., and Hirahara, K
  • Organizer: The 52nd Annual Meeting of The Japanese Society for Immunology
  • Int'l Joint Research
• [Presentation] Suppression of type I interferon signaling in myeloid cells by autoantibodies in severe COVID-19 patients (2024)
  • Author(s): Sasaki, A., Aoki, A., Iwamura, C., Kiuchi, M., Tsuji, K., Hishiya, T., Hirasawa, R., Kokubo, K., Onodera, A., Suzuki, T., Nakayama, T., and Hirahara, K
  • Organizer: The 52nd Annual Meeting of The Japanese Society for Immunology
  • Int'l Joint Research
• [Presentation] Amphiregulin-producing T helper 2 cells facilitate esophageal fibrosis of eosinophilic esophagitis (2024)
  • Author(s): Kaneko, T., Iwamura, C., Kurosugi, A., Kiuchi, M., Nakayama, T., and Hirahara, K
  • Organizer: The 52nd Annual Meeting of The Japanese Society for Immunology
  • Int'l Joint Research
• [Presentation] Pathological tissue inflammatory memories (2024)
  • Author(s): Hirahara, K
  • Organizer: 5th CSI/JSI/KAI Joint Symposium on Immunology “Frontier in Immunology Research in the Aftermath of the Pandemic”
  • Int'l Joint Research / Invited
• [Presentation] Thioredoxin-interacting protein is essential for memory T cell formation via the regulation of the redox metabolism (2024)
  • Author(s): Kokubo, K., Kiuchi, M., Hirahara, K., and Nakayama, T
  • Organizer: 5th CSI/JSI/KAI Joint Symposium on Immunology “Frontier in Immunology Research in the Aftermath of the Pandemic”
  • Int'l Joint Research
• [Presentation] IgM-mediated modulation of AIM: Enhancing clearance of biological waste (2024)
  • Author(s): Satoko Arai
  • Organizer: The International Symposium on Resolution of Inflammation
• [Presentation] 慢性アレルギー炎症難治化における病原性T細胞を中心とした細胞間ネットワークの役割 (2023)
  • Author(s): 平原潔
  • Organizer: セッション 第10回JCRベーシックリサーチカンファレンス
  • Invited
• [Presentation] 喘息病態におけるTertiary Lymphoid Structureの病的役割-治療ターゲットとしての組織炎症記憶- (2023)
  • Author(s): 平原潔
  • Organizer: Scientific Exchange Meeting in Kyoto
  • Invited
• [Presentation] 記憶T細胞を起点とした「神経免疫連関」による病的かゆみの病態形成機構 (2023)
  • Author(s): 平原潔
  • Organizer: シンポジウム 第96回日本生化学会大会
  • Invited
• [Presentation] Pathological tissue inflammatory memories - Immune-neuro interaction shapes the transformation of inflamed tissue - (2023)
  • Author(s): Hirahara, K
  • Organizer: The 32nd Hot Spring Harbor International Symposium Recent Advances in Cell Biology and Immunology 2023
  • Invited
• [Presentation] 眼瞼結膜における「神経-免疫連関」を介したかゆみの病態形成機構 (2023)
  • Author(s): 平原潔
  • Organizer: 第72回日本アレルギー学会学術大会
  • Invited
• [Presentation] 治療学研究へのいざない - SARS-CoV2感染の重症化機構から慢性炎症疾患の難治性病態まで- (2023)
  • Author(s): 平原潔
  • Organizer: 石巻赤十字病院 感染症セミナー
  • Invited
• [Presentation] 組織炎症記憶による慢性炎症の病態形成機構 (2023)
  • Author(s): 平原潔
  • Organizer: シンポジウム 第53回日本腎臓学会西部学術大会
  • Invited
• [Presentation] 病原性記憶T細胞の多様性とアレルギー性炎症の難治性病態について－組織線維化から病的かゆみまで－ (2023)
  • Author(s): 平原潔
  • Organizer: 特別公演 Online Science Club
  • Invited
• [Presentation] 疫細胞の組織への常在化と慢性炎症の難治化－組織常在性記憶T細胞と異所性リンパ組織の病的役割－ (2023)
  • Author(s): 平原潔
  • Organizer: 講演 第49回佐島シンポジウム
  • Invited
• [Presentation] 病原性T細胞と異所性リンパ組織の相互作用による病態形成機構について (2023)
  • Author(s): 平原潔
  • Organizer: シンポジウム 第4回日本喘息学会総会学術大会
  • Invited
• [Presentation] 「治療学研究へのいざない - 病原性T細胞の機能的多様性が誘導する様々な難治病態 -」 (2023)
  • Author(s): 平原潔
  • Organizer: 特別講演 第71回文月会 総会/講演会/懇親会
  • Invited
• [Presentation] 慢性炎症難治化における細胞間ネットワーク－病原性T細胞と好酸球のcross-talkによる組織線維化機構－ (2023)
  • Author(s): 平原潔
  • Organizer: 溜池カンファレンス2023
  • Invited
• [Presentation] 『治療学研究へのいざない - 病原性T細胞の機能的多様性が誘導する様々な難治病態 - 』 (2023)
  • Author(s): 平原潔
  • Organizer: 特別講演 第113回新潟内分泌代謝同好会
  • Invited
• [Presentation] COVID-19における血管内皮障害・血小板活性化のメカニズム (2023)
  • Author(s): 平原潔
  • Organizer: 第65回日本小児神経学会
  • Invited
• [Presentation] ST2+ memory Th2 cells shape the intractable pathogenesis of chronic inflammation - Interleukin-33-neuropeptide CGRP axis induces conjunctival itch - (2023)
  • Author(s): Hirahara, K
  • Organizer: The Laboratory of Immunology Weekly Seminar Series
  • Invited
• [Presentation] Immune-neuro interaction shapes the pathology of intractable allergic diseases (2023)
  • Author(s): Hirahara, K
  • Organizer: シンポジウム International Symposium for Future Mucosal Vaccines: Safeguards and Innovations against Infectious Diseases
  • Invited
• [Presentation] AIM/CD5L分子表面ネガティブ・チャージ・クラスターの機能解析 (2023)
  • Author(s): 石井和浩, 新井郷子, 宮崎徹
  • Organizer: ポスターセッション 第46回日本分子生物学会年会
• [Presentation] Facilitation of disease repair through phagocytic removal of different inflammatory organic wastes by AIM/CD5L (2023)
  • Author(s): Toru Miyazaki, Satoko Arai
  • Organizer: Poster Presentation IUIS 2023, 18th International Congress of Immunology
  • Int'l Joint Research
• [Presentation] 血中タンパク質AIMの炎症性疾患における役割とその治療・診断応用 (2023)
  • Author(s): 新井郷子
  • Organizer: 第96回日本生化学会大会
• [Presentation] 腎結石症改善に向けた最新知見 －血中タンパク質AIMの結石抑制における新たな役割の発見－ (2023)
  • Author(s): 新井郷子
  • Organizer: 第14回日本臨床一般検査学会、第20回スキルアップ講習会
• [Presentation] Facilitation of disease repair through phagocytic removal of different inflammatory elements by AIM/CD5L (2023)
  • Author(s): Toru Miyazaki, Satoko Arai
  • Organizer: 3rd RESOLUTION DAYS
  • Int'l Joint Research
• [Presentation] 炎症収束学・その先へ: 慢性炎症と炎症性組織修復レジリエンスの統合的理解 多様性から迫る腸管恒常性維持機構と炎症性腸疾患病態の理解 (2023)
  • Author(s): 三上 洋平, 佐藤 俊朗, 金井 隆典
  • Organizer: シンポジウム 第96回日本生化学会大会
• [Presentation] IBDのTreat to Targetの実際-治療選択のポイント 潰瘍性大腸炎に対する抗TNF-α抗体製剤セカンドラインの有効性に関する検討 (2023)
  • Author(s): 清原 裕貴, 三上 洋平, 金井 隆典
  • Organizer: パネルディスカッション JDDW 2023 (Japan Digestive Disease Week 2023) KOBE
• [Presentation] 疾患層別化、治療応用につながる免疫疾患の病態理解 1細胞遺伝子発現解析を用いた消化管線維芽細胞の多様性の理解 (2023)
  • Author(s): 三上 洋平, 高田 祐明, 萩原 裕也, 角田 潤也, 水島 一郎, 入江 江美, 石原 利乃, 佐藤 俊朗, 金井 隆典
  • Organizer: シンポジウム 第51回日本臨床免疫学会総会
  • Invited
• [Presentation] １細胞遺伝子発現解析を用いた消化管の機能解析 (2023)
  • Author(s): 三上洋平，高田祐明，岩田賢太郎，入江江美，角田潤哉，水島一郎，萩原裕也，石原利乃，金井隆典
  • Organizer: ワークショップ 第60回日本消化器免疫学会総会
• [Presentation] Assessment of mucosal inflammation for Crohn’s disease: safety and potential of intraoperative complete enteroscopy (ICE) (2023)
  • Author(s): Yohei MIKAMI, Koji OKABAYASHI, Takanori KANAI
  • Organizer: パネルディスカッション・国際セッション 第105回日本消化器内視鏡学会総会
  • Int'l Joint Research
• [Presentation] Enrichement of type I interferon signalling in the colonic ILC2 under inflammatory condition (2023)
  • Author(s): Yohei Mikami, Emi Irie, Rino Ishihara, Ichiro Mizushima, Takanori Kanai
  • Organizer: Poster Presentation IMMUNOLOGY2023 AAI Annual Meeting
  • Int'l Joint Research
• [Book] 臨床免疫・アレルギー科 (2023)
  • Author(s): 尾上美樹、岡野美樹子、木内政宏、海老原伸行、中山俊憲、平原潔
  • Total Pages: 7
  • Publisher: 科学評論社
• [Remarks] 千葉大学大学院医学研究院 免疫発生学HP
  • URL: https://www.m.chiba-u.jp/dept/meneki/
• [Funded Workshop] The International Symposium on Resolution of Inflammation（2024年1月18日、幕張メッセ、千葉) (2024)