Development of new therapy for eosinophilic gastrointestinal diseases targeting the regulation of mucosal barrier
| Project/Area Number |
19K08480
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 53010:Gastroenterology-related
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| Research Institution | Hyogo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
福井 広一 兵庫医科大学, 医学部, 准教授 (60378742)
三輪 洋人 兵庫医科大学, 医学部, 教授 (80190833)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 好酸球性消化管疾患 / 細胞間接着装置 / タイト結合 / クローディン |
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| Outline of Research at the Start |
本研究は，未だ不明な点の多い消化管粘膜バリア機能の破綻がみられる疾患群，特に好酸球性消化管疾患における粘膜バリア機能が破綻する機序およびその制御を明らかにすることを目的とする．全く明らかとなっていない食道の扁平上皮粘膜層（顆粒層，有棘層，基底層）の各層の役割の違いに着目し，好酸球浸潤の程度と各層におけるタイト結合蛋白発現の相関を解析する．さらに上皮由来サイトカインであるIL-25, IL-32, IL-33及びTSLPやグループ2自然リンパ球（ILC2）が産生するサイトカインの粘膜上皮のバリア機能への役割を解析することでバリア機能を制御することによる治療応用の可能性が期待される．
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| Outline of Final Research Achievements |
Esophageal epithelial barrier function, and mast cell infiltration, as well as chemokine levels in eosinophilic esophagitis (EoE) patients before and after treatment were evaluate. Esophageal Epithelial infiltration of mast cells, and permeability were increased in EoE patients. Levels of IL-13, calpain-14, and eotaxin-3 mRNAs were upregulated, while filaggrin, SPINK7, and involucrin mRNAs were downregulated in EoE patients. In patients achieving histologic remission diagnosed by eosinophil counts, a subset of EoE patients with unchanged permeability after treatment showed increased mast cell infiltration, IL-13, calpain-14, filaggrin and SPINK7 with decreased eotaxin-3 and involucrin. Other EoE patients with decreased permeability displayed decreased eotaxin-3, and mast cell infiltration, and increased, filaggrin, and SPINK7. Increased permeability of the esophagus in EoE patients without eosinophil infiltration after treatment was associated with mast cell infiltration.
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| Academic Significance and Societal Importance of the Research Achievements |
好酸球性食道炎は希少疾患であるが，最近日本においても増加傾向にあり，その病態は不明な点が多い．完全に食道の炎症が改善していない状況で治療を中断すると再度炎症が発生して症状に悩まされることになる．これまで食道粘膜内の好酸球浸潤が改善することで治癒判定がなされているが，好酸球浸潤が改善したあとも食道粘膜の透過性が上昇し，肥満細胞浸潤が見られることが明らかとなり，今後治療の判定方法を再考する必要がある．
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Report
(4 results)
Research Products
(5 results)
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[Presentation] Effect of treatment on esophageal epithelial barrier function and inflammation in eosinophilic esophagitis2021
Author(s)
Junji Chen, Tadayuki Oshima, Keisuke Nakai, Yoshitaka Kitayama, Ken Hara, Akio Tamura, Masashi Fukushima, Takuya Okugawa, Toshihiko Tomita, Hirokazu Fukui, Hiroto Miwa
Organizer
Asian Pacific Digestive Week (APDW) 2021
Related Report
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