Elucidation of house dust mite-induced intestinal epithelial barrier dysfunction in the development of chronic enteropathy in dogs

• Project/Area Number: 17K08099
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Veterinary medical science
• Research Institution: Tokyo University of Agriculture and Technology
• Principal Investigator: Ohmori Keitaro 東京農工大学, (連合)農学研究科(研究院), 講師 (20466915)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: ハウスダストマイト / 犬 / 慢性腸症 / サイトカイン / インフラマソーム / 消化管 / 腸上皮バリア

Outline of Final Research Achievements

House dust mite (HDM) is an environmental allergen ubiquitously present indoors, causing allergic inflammation in dogs. However, whether HDM allergens are detected in the gastrointestinal (GI) tract of dogs and their contribution to the development of chronic enteropathy (CE) remain unclear. The purposes of this study were to determine the presence of HDM allergens in the GI tract of dogs with CE, and to elucidate the effect of HDM on IL-1beta and NLRP3 expression in canine macrophages. HDM allergens were detected in the gastric and duodenal fluids of laboratory healthy dogs and dogs with CE and feces of all dogs examined. HDM allergens in the duodenal and colonic mucosae were significantly higher in dogs with CE than in laboratory healthy dogs. HDM induced expressions of nlrp3 and il-1beta mRNA and IL-1beta protein in canine macrophages. HDM allergens present in the GI tract may be involved in the pathogenesis of CE, promoting IL-1beta expression in the intestinal mucosa.

Academic Significance and Societal Importance of the Research Achievements

環境アレルゲンであるHDMは、健常犬および慢性腸症の犬を含め、家庭で飼育されている犬に幅広く経口摂取されるが、腸上皮バリア機能が減弱した慢性腸症の犬の腸粘膜では、HDMアレルゲンが腸粘膜内に侵入し、腸粘膜に存在するマクロファージのNLRP3インフラマソームを活性化することでIL-1betaの産生を誘導する可能性が明らかになった。本研究により、HDMが慢性腸症の犬の消化管において、自然免疫系を活性化することで慢性的な腸炎を発症させる新たな病態が明らかになった。

Research Products

• [Journal Article] Effects of a selective casein kinase 1δ and ε inhibitor on FcεRI expression and IgE-mediated immediate-type cutaneous reactions in dogs (2019)
  • Author(s): Ohno H, Takahashi K, Yanuma N, Ogawa M, Hasegawa A, Sugita K, Kawano K, Sasaki K, Shirai J, Nagaoka K, Ohmori K.
  • Journal Title: Journal of Veterinary Medical Science Volume: 81 Issue: 11 Pages: 1680-1684
  • DOI: 10.1292/jvms.18-0756
  • NAID: 130007757464
  • ISSN: 0916-7250, 1347-7439
  • Peer Reviewed / Open Access
• [Journal Article] Oral faecal microbiota transplantation for the treatment of Clostridium difficile-associated diarrhoea in a dog: a case reporｔ (2019)
  • Author(s): Sugita K, Yanuma N, Ohno H, Takahashi K, Kawano K, Morita H, Ohmori K.
  • Journal Title: BMC Vet Res Volume: 15 Issue: 1 Pages: 11-11
  • DOI: 10.1186/s12917-018-1754-z
  • Peer Reviewed / Open Access
• [Journal Article] Influence of glucocorticoids on time-of-day-dependent variations in IgE-, histamine-, and platelet-activating factor-mediated systemic anaphylaxis in different mouse strains (2018)
  • Author(s): Hasegawa A, Watanabe M, Osada H, Ogawa M, Ohno H, Yanuma N, Sasaki K, Shimoda M, Shirai J, Ohmori K.
  • Journal Title: Biochem Biophys Res Commun Volume: 495(3) Issue: 3 Pages: 2184-2188
  • DOI: 10.1016/j.bbrc.2017.12.099
  • Peer Reviewed
• [Journal Article] Effect of interleukin-1β on occludin mRNA expression in the duodenal and colonic mucosa of dogs with inflammatory bowel disease. (2018)
  • Author(s): Ogawa M, Osada H, Hasegawa A, Ohno H, Yanuma N, Sasaki K, Shimoda M, Shirai J, Kondo H, Ohmori K.
  • Journal Title: J Vet Intern Med Volume: 印刷中 Issue: 3 Pages: 1019-1025
  • DOI: 10.1111/jvim.15117
  • Peer Reviewed / Open Access
• [Journal Article] Expression of epithelial cell-derived cytokine genes in the duodenal and colonic mucosae of dogs with chronic enteropathy (2017)
  • Author(s): Osada H, Ogawa M, Hasegawa A, Nagai M, Shirai J, Sasaki K, Shimoda M, Itoh H, Kondo H, Ohmori K.
  • Journal Title: Journal of Veterinary Medical Science Volume: 79 Issue: 2 Pages: 393-397
  • DOI: 10.1292/jvms.16-0451
  • NAID: 130005397080
  • ISSN: 0916-7250, 1347-7439
  • Peer Reviewed / Open Access
• [Presentation] 国内の犬における食事反応性腸症および炎症性腸疾患の臨床的特徴に関する回顧的研究 (2020)
  • Author(s): 古川林太郎, 高橋佳穂, 廣川真凜, 宮島柾生, 伊藤博, 大森啓太郎
  • Organizer: 第16回日本獣医内科学アカデミー学術大会
• [Presentation] 慢性腸症の犬の消化管内に存在するハウスダストマイトの作用解析：マクロファージからのIL-1beta産生作用 (2019)
  • Author(s): 高橋佳穂、矢沼菜々子、大野光、廣川真凜、宮島柾生、杉田浩児、佐々木一昭、白井淳資、大森啓太郎
  • Organizer: 第162回日本獣医学会学術集会
• [Presentation] Fecal microbiota transplantation for the treatment of protein-losing enteropathy secondary to inflammatory bowel disease in two dogs (2019)
  • Author(s): Sugita K, Takahashi K, Ogawa M, Hasegawa A, Yanuma N, Ohno H, Kawano K, Ohmori K.
  • Organizer: Asian Meeting of Animal Medical Specialties 2019
  • Int'l Joint Research
• [Presentation] Presence of house dust mite in the gastrointestinal tract of dogs with chronic enteropathy: a potential inducer of IL-1beta from macrophages (2019)
  • Author(s): Takahashi K, Yanuma N, Ohno H, Hirokawa M, Miyajima M, Sugita K, Sasaki K, Shirai J, Ohmori K.
  • Organizer: Asian Meeting of Animal Medical Specialties 2019
  • Int'l Joint Research
• [Presentation] Clostridium difficileが検出された慢性大腸性下痢に対し経口糞便移植療法を行った犬の1例 (2019)
  • Author(s): 杉田浩児、矢沼菜々子、大野光、髙橋佳穂、川野浩志、森田英利、大森啓太郎
  • Organizer: 第15回日本獣医内科学アカデミー学術大会
• [Presentation] 慢性腸症の犬の消化管内におけるハウスダストマイトの存在 (2018)
  • Author(s): 矢沼菜々子、大野光、高橋佳穂、小川美聡、長谷川絢奈、杉田浩児、佐々木一昭、白井淳資、大森啓太郎
  • Organizer: 第161回日本獣医学会学術集会
• [Presentation] 犬の炎症性腸疾患の結腸粘膜におけるIL-1betaの発現が腸管上皮細胞の密着結合に及ぼす影響 (2017)
  • Author(s): 小川美聡、長田大翔、長谷川絢奈、大野光、矢沼菜々子、佐々木一昭、下田 実、白井淳資、近藤広孝、大森啓太郎
  • Organizer: 第160回日本獣医学会学術集会
• [Presentation] マウス系統による全身性アナフィラキシー日内変動の違い (2017)
  • Author(s): 長谷川絢奈、渡邉美和、長田大翔、小川美聡、大野光、矢沼菜々子、佐々木一昭、下田実、白井淳資、大森啓太郎
  • Organizer: 第160回日本獣医学会学術集会
• [Presentation] Imbalance of interleukin-1beta and interleukin-1 receptor antagonist attenuates gene expression of occludin, a tight junction component, in the colonic mucosa of dogs with inflammatory bowel disease (2017)
  • Author(s): Ogawa M, Osada H, Hasegawa A, Ohno H, Yanuma N, Sasaki K, Shimoda M, Shirai J, Kondo H, Ohmori K.
  • Organizer: Asian Meeting of Animal Medicine Specialties 2017
  • Int'l Joint Research