Antigen presenting cell mediated regulation of intestinal inflammation

• Project/Area Number: 18K15128
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Harusato Akihito 京都府立医科大学, 医学(系)研究科(研究院), 助教 (30434509)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: IL-36 / 食物アレルギー / 大腸がん / マイクロプラスチック / 2型サイトカイン / ２型サイトカイン / 腸内細菌 / 大腸 / 抗原提示細胞 / MDSC / Erdr-1 / 炎症性腸疾患 / 腸管バリア / 腸管樹状細胞 / サイトカイン / 腸炎

Outline of Final Research Achievements

In this project, we uncovered that Notch-2 dependent CD103+CD11b+ dendritic cells is critical for IL-36 mediated induction of IL-23 (PNAS 2018). We also discovered that IL-36 is involved in the pathogenesis of food allergy for the first time (Nutrients 2022). Further, we found that microbiota exposure in early life plays a key role in the development of intestinal immunity (Cancer Immunol Res 2019). Finally we reported the impact of particulate microplastics generated from polyethylene terephthalate on gut pathology and immunity (iScience 2023).

Academic Significance and Societal Importance of the Research Achievements

新規IL-1ファミリーに属するIL-36が腸管免疫機構で果たしている役割について、炎症・アレルギーといった側面からそのメカニズムを明らかに出来た点に大きな学術的な意義があった。研究期間後半に実施した研究は、コロナ禍の影響により進捗が大きく遅延した一方で、結果的には、腸内細菌、食品添加剤、マイクロプラスチックといった環境修飾因子と疾病について、社会的意義のある研究を報告できたと考えられる。

Research Products

• [Int'l Joint Research] INSERM(フランス)
• [Int'l Joint Research] INSERM(フランス)
• [Int'l Joint Research] Georgia State University(米国)
• [Int'l Joint Research] INSERM(フランス)
• [Int'l Joint Research] Georgia State University/University of Michigan/Emory University(米国)
• [Int'l Joint Research] INSERM U1016(フランス)
• [Int'l Joint Research] Georgia State University/Emory University/University of Michigan(米国)
• [Int'l Joint Research] Universite Clermont Auvergne(フランス)
• [Journal Article] Impact of particulate microplastics generated from polyethylene terephthalate on gut pathology and immune microenvironments (2023)
  • Author(s): Harusato Akihito、Seo Wooseok、Abo Hirohito、Nakanishi Yoshitaka、Nishikawa Hiroyoshi、Itoh Yoshito
  • Journal Title: iScience Volume: 26 Issue: 4 Pages: 106474-106474
  • DOI: 10.1016/j.isci.2023.106474
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Dietary Emulsifiers Exacerbate Food Allergy and Colonic Type 2 Immune Response through Microbiota Modulation (2022)
  • Author(s): Harusato Akihito、Chassaing Benoit、Dauriat Charl?ne J. G.、Ushiroda Chihiro、Seo Wooseok、Itoh Yoshito
  • Journal Title: Nutrients Volume: 14 Issue: 23 Pages: 4983-4983
  • DOI: 10.3390/nu14234983
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 腸管免疫細胞のクロストーク (2021)
  • Author(s): 春里暁人、伊藤義人
  • Journal Title: 京府医大誌. Volume: 130 (4) Pages: 287-295
  • Peer Reviewed / Open Access
• [Journal Article] Erythroid differentiation regulator-1 induced by microbiota in early life drives intestinal stem cell proliferation and regeneration (2020)
  • Author(s): Abo Hirohito、Chassaing Benoit、Harusato Akihito、Quiros Miguel、Brazil Jennifer C.、Ngo Vu L.、Viennois Emilie、Merlin Didier、Gewirtz Andrew T.、Nusrat Asma、Denning Timothy L.
  • Journal Title: Nature Communications Volume: 11 Issue: 1 Pages: 513-513
  • DOI: 10.1038/s41467-019-14258-z
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Early-Life Microbiota Exposure Restricts Myeloid-Derived Suppressor Cell Driven Colonic Tumorigenesis (2019)
  • Author(s): Harusato Akihito、Viennois Emilie、Etienne-Mesmin Lucie、Matsuyama Shingo、Abo Hirohito、Osuka Satoru、Lukacs Nicholas W.、Naito Yuji、Itoh Yoshito、Li Jian-Dong、Merlin Didier、Gewirtz Andrew T.、Denning Timothy L.
  • Journal Title: Cancer Immunology Research Volume: 7 Issue: 4 Pages: 544-551
  • DOI: 10.1158/2326-6066.cir-18-0444
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Combined IL-2 Immunocomplex and Anti-IL-5 mAb Treatment Expands Foxp3+ Treg Cells in the Absence of Eosinophilia and Ameliorates Experimental Colitis (2019)
  • Author(s): Abo Hirohito、Flannigan Kyle L.、Geem Duke、Ngo Vu L.、Harusato Akihito、Denning Timothy L.
  • Journal Title: Frontiers in Immunology Volume: 10
  • DOI: 10.3389/fimmu.2019.00459
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A cytokine network involving IL-36γ, IL-23, and IL-22 promotes antimicrobial defense and recovery from intestinal barrier damage (2018)
  • Author(s): Ngo Vu L.、Abo Hirohito、Maxim Estera、Harusato Akihito、Geem Duke、Medina-Contreras Oscar、Merlin Didier、Gewirtz Andrew T.、Nusrat Asma、Denning Timothy L.
  • Journal Title: Proceedings of the National Academy of Sciences Volume: 115 Issue: 22
  • DOI: 10.1073/pnas.1718902115
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Heme oxygenase-1 prevents murine intestinal inflammation (2018)
  • Author(s): Takagi Tomohisa、Naito Yuji、Mizushima Katsura、Hirai Yasuko、Harusato Akihito、Okayama Tetsuya、Katada Kazhuhiro、Kamada Kazuhiro、Uchiyama Kazuhiko、Handa Osamu、Ishikawa Takeshi、Itoh Yoshito
  • Journal Title: Journal of Clinical Biochemistry and Nutrition Volume: 63 Issue: 3 Pages: 169-174
  • DOI: 10.3164/jcbn.17-133
  • ISSN: 0912-0009, 1880-5086
  • Peer Reviewed
• [Presentation] Early life microbiota controls CXCR2 mediated myeloid derived suppressor cell driven colitis-associated tumorigenesis (2019)
  • Author(s): Akihito Harusato
  • Organizer: International Congress of Mucosal Immunology
  • Int'l Joint Research
• [Presentation] Dietary Emulsifier Polysorbate-80 Exacerbates Experimental Food Allergy with Increased Expressions of Colonic Th2 Cytokines (2019)
  • Author(s): Akihito Harusato, Benoit Chassaing
  • Organizer: 第48回日本免疫学会学術集会
• [Presentation] 新生仔期腸内細菌叢が大腸発癌に及ぼす影響に関する検討 (2019)
  • Author(s): 春里暁人
  • Organizer: 第57回日本消化器免疫学会総会
• [Presentation] Early life microbiota exposure attenuates colonic tumorigenesis (2018)
  • Author(s): Akihito Harusato
  • Organizer: Cleveland International Digestive Education and Science Symposium 2018
• [Presentation] Interleukin-36γによる腸管バリア維持機構に関する検討 (2018)
  • Author(s): 春里暁人
  • Organizer: 第55回日本消化器免疫学会
• [Remarks] Early-Life Microbiota Restricts Colon Cancer
  • URL: https://news.gsu.edu/2019/03/13/early-life-exposure-to-microbiota-restricts-colon-cancer-later-in-life-study-finds/
• [Remarks] New Cytokine Network Can Repair Tissue Damage
  • URL: https://news.gsu.edu/2018/05/15/new-cytokine-network-can-repair-tissue-damage-caused-in-the-intestine-study-finds/