Essential role of interleuikin-33-induced innate lymphoid cells in development of eosinophilic esophagitis in mice

• Project/Area Number: 26870378
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Collagenous pathology/Allergology; Gastroenterology
• Research Institution: Shimane University
• Principal Investigator: Oshima Naoki 島根大学, 医学部, 助教 (10403461)
• Research Collaborator: Yoshikazu Kinoshita 島根大学, 医学部, 教授 (30243306)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 好酸球性食道炎 / アレルギー / IL-33 / ILC2 / NH細胞 / 自然リンパ球 / 好酸球

Outline of Final Research Achievements

Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder of the esophagus characterized by mucosal infiltration of eosinophils. Interleukin (IL)-33 is a member of the IL-1 cytokine family that is constitutively expressed in epithelial cells. Epithelial-derived IL-33 induces innate lymphoid cell group 2 (ILC2) activities in various organs, which subsequently activates Th2 cytokines and leads to development of eosinophil-related allergic diseases. However, little is known regarding the roles of IL-33 and ILC2 activity induced by it in the pathogenesis of EoE. In the present study, several experimental protocols were designed to clarify these issues.　 Our results clearly show that IL-33-induced ILC2 cell activity leads to infiltration of esophageal mucosa by eosinophils via production of Th2- and allergy-related cytokines, which may play an important role in EoE development.

Research Products

• [Journal Article] Epidermal differentiation complex protein involucrin is down-regulated in eosinophilic esophagitis. (2017)
  • Author(s): Oshima N, Ishihara S, Ishimura N, Kinoshita Y.
  • Journal Title: Esophagus Volume: 14（3） Pages: 171-177
  • NAID: 40021166323
  • Peer Reviewed
• [Journal Article] Similarities and differences among eosinophilic esophagitis, proton-pump inhibitor-responsive esophageal eosinophilia, and reflux esophagitis: comparisons of clinical, endoscopic, and histopathological findings in Japanese patients. (2017)
  • Author(s): Jiao D, Ishimura N, Oshima N, Ishihara S, Kinoshita Y.
  • Journal Title: J Gastroenterol Volume: 52（2） Pages: 203-210
  • Peer Reviewed
• [Journal Article] Specific locations of linear furrows in patients with esophageal eosinophilia. (2017)
  • Author(s): Okimoto E, Ishimura N, Oshima N, Ishihara S, Kinoshita Y.
  • Journal Title: Dig Endosc Volume: 29(1) Pages: 49-56
  • Peer Reviewed
• [Journal Article] Specific locations of linear furrows in patients with esophageal eosinophilia (2017)
  • Author(s): Okimoto E, Ishimura N, Okada M, Izumi D, Mikami H, Aimi M, Tanimura T, Mishiro T, Oshima N, Ishikawa N, Ishihara S, Adachi K, Maruyama R, Kinoshita Y
  • Journal Title: Digestive Endoscopy Volume: 29 Issue: 1 Pages: 49-56
  • DOI: 10.1111/den.12706
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Recent Progress in the Research of Eosinophilic Esophagitis and Gastroenteritis. (2016)
  • Author(s): Kinoshita Y, Ishimura N, Oshima N, Mikami H, Okimoto E, Jiao DJ, Ishihara S.
  • Journal Title: Digestion Volume: 93 Issue: 1 Pages: 7-12
  • DOI: 10.1159/000441668
  • Peer Reviewed / Open Access
• [Journal Article] 好酸球性消化管障害 －好酸球性食道炎と好酸球性胃腸炎－ (2015)
  • Author(s): 大嶋直樹、木下芳一
  • Journal Title: アレルギーの臨床 Volume: 35 Pages: 100-105
• [Journal Article] 臓器病変を伴う好酸球増多症 好酸球性胃腸炎 (2015)
  • Author(s): 大嶋直樹、木下芳一
  • Journal Title: 診断と治療 Volume: 103 Pages: 665-669
• [Presentation] Essential role of interleuikin-33-induced innate lymphoid cells in development of eosinophilic esophagitis in mice (2017)
  • Author(s): Naoki Oshima, Shunji Ishihara, Kousaku Kawashima, Hiroki Sonoyama, Noritsugu Yamashita, Nobuhiko Fukuba, Yoshiyuki Mishima, Norihisa Ishimura, Ichiro Moriyama, Yoshikazu Kinoshita
  • Organizer: UEG Week 2017
  • Int'l Joint Research
• [Presentation] 好酸球性食道炎の病態形成にIL-33は関与するのか？ (2014)
  • Author(s): 大嶋直樹、石原俊治、木下芳一
  • Organizer: 第51回日本消化器免疫学会総会
  • Place of Presentation: 京都大学医学部芝蘭会館
  • Year and Date: 2014-07-10 – 2014-07-11
• [Presentation] IL-33を標的とした好酸球性食道炎の病態機序の解明 (2014)
  • Author(s): 大嶋直樹、石村典久、木下芳一
  • Organizer: 第100回日本消化器病学会総会
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2014-04-23 – 2014-04-26
• [Book] 好酸球性食道疾患診療ガイド（木下芳一編） (2014)
  • Author(s): 大嶋 直樹 他
  • Total Pages: 103
  • Publisher: 南江堂