Investigation of the role of mucosal inductive immune system via indigenous bactria and dietary antigens

• Project/Area Number: 26460969
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Osaka University
• Principal Investigator: Iijima Hideki 大阪大学, 医学系研究科, 准教授 (90444520)
• Co-Investigator(Kenkyū-buntansha): 辻井 正彦 大阪大学, 医学系研究科, 招へい教授 (40303937) ; 新崎 信一郎 大阪大学, 医学系研究科, 助教 (60546860)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 炎症性腸疾患 / パイエル板 / 粘膜免疫誘導組織 / 腸内細菌 / 粘膜免疫 / NSAID起因性小腸潰瘍 / ケモカインレセプター / 小腸潰瘍 / インドメタシン / 腸管粘膜障害 / immunonutrition / CCR7 / 小腸パイエル板

Outline of Final Research Achievements

Ulceration of the small intestine is induced when mice were intraperitoneally injected with indomethacine. We found chemokine receptor CCR7-deficient mice show worsening of the ulcer area in the small intestine. In addition, the population of CD103-positive dendritic cells which have a role for the induction of regulatory T cells was decreased in CCR7-deficient mice.
In contrast, ulcer area was significantly decreased in the wild-type mice orally administered nutritional therapy containing RNA and other nutrients (Impact(R)) or elementary diet with amino-acids. In mice treated with Impact showed significantly increased CD103-positive dendritic cells. These results indicate the importance of CD103-positive dendritic cells and immune-nutritional therapy and they can be effective to regulate mucosal immunity-associated intestinal inflammation.

Research Products

• [Journal Article] Leucine-rich Alpha-2 Glycoprotein is a Serum Biomarker of Mucosal Healing in Ulcerative Colitis (2017)
  • Author(s): Shinzaki, S., Matsuoka, K., Iijima, H., Mizuno, S., Serada, S., Fujimoto, M., Arai, N. Koyama, N., Morii, E., Watanabe, M., Hibi, T., Kanai, T., Takehara, T., Naka, T.
  • Journal Title: Journal of Crohn's and Colitis Volume: 11(1) Issue: 1 Pages: 84-91
  • DOI: 10.1093/ecco-jcc/jjw132
  • Peer Reviewed
• [Journal Article] Age at onset is associated with the seasonal pattern of onset and exacerbation in inflammatory bowel disease (2017)
  • Author(s): Araki, M, Shinzaki, S., Yamada, T., Arimitsu S., Komori, M., Shibukawa, N., Mukai A., Nakajima, S., Kinoshita, K., Kitamura, S., Murayama, Y., Ogawa H., Yasunaga Y, Oshita, M., Fukui, H., Masuda E., Tsujii, M., Hiyama, S., Inoue, T., Iijima, H., Takehara, T.
  • Journal Title: Journal of Gastroenterology Volume: 印刷中 Issue: 11 Pages: 1149-1157
  • DOI: 10.1007/s00535-017-1313-6
  • Peer Reviewed
• [Journal Article] Indigo Naturalis ameliorates murine dextran sodium sulfate-induced colitis via aryl hydrocarbon receptor activation. (2017)
  • Author(s): Kawai S, Iijima H, Shinzaki S, Hiyama S, Yamaguchi T, Araki M, et al.
  • Journal Title: J Gastroenterol. Volume: 印刷中 Issue: 8 Pages: 904-919
  • DOI: 10.1007/s00535-016-1292-z
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] N-Acetylglucosaminyltransferase V exacerbates murine colitis with macrophage dysfunction and enhances colitic tumorigenesis. (2016)
  • Author(s): Shinzaki S, Ishii M, Fujii H, Iijima H, Wakamatsu K, Kawai S, Shiraishi E, Hiyama S, Inoue T, Hayashi Y, Kuwahara R, Takamatsu S, Kamada Y, Morii E, Tsujii M, Takehara T, Miyoshi E.
  • Journal Title: J Gastroenterol Volume: 51 Issue: 4 Pages: 357-69
  • DOI: 10.1007/s00535-015-1112-x
  • Peer Reviewed
• [Journal Article] N-Acetylglucosaminyltransferase V exacerbates murine colitis with macrophage dysfunction and enhances colitic tumorigenesis. (2016)
  • Author(s): Shinzaki S, Ishii M, Fujii H, Iijima H, Wakamatsu K, Kawai S, Shiraishi E, Hiyama S, Inoue T, Hayashi Y, Kuwahara R, Takamatsu S, Kamada Y, Morii E, Tsujii M, Takehara T, Miyoshi E.
  • Journal Title: J Gastroenterol. Volume: 51 Issue: 4 Pages: 357-369
  • DOI: 10.1007/s00535-015-1119-3
  • Peer Reviewed
• [Journal Article] Lypd8 promotes the segregation of flagellated microbiota and colonic epithelia. (2016)
  • Author(s): Okumura R, Kurakawa T, Nakano T, Kayama H, Kinoshita M, Motoka D, Gotoh K, Kimura T, Kamiyama N, Kusu T, Ueda Y, Wu H, Iijima H, Barman S, Osawwa H, Matsuno H, Nishimura J, Ohba Y, Nakamura S, Iida T, Yamamoto M, Umemoto E, Sano K, and Takeda K
  • Journal Title: Nature Volume: 532 Issue: 7597 Pages: 117-121
  • DOI: 10.1038/nature17406
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Narrow-band imaging with magnifying endoscopy for Peyer's patches is useful in predicting the recurrence of remissive patients with ulcerative colitis. (2016)
  • Author(s): Hiyama S, Iijima H, Kawai S, Mukai A, Shiraishi E, Iwatani S, et al.
  • Journal Title: Intest Res. Volume: 14(4) Issue: 4 Pages: 314-21
  • DOI: 10.5217/ir.2016.14.4.314
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Core Fucosylation on T cells, Required for Activation of T-cell Receptor Signaling and Induction of Colitis in Mice, is Increased in Patients with Inflammatory Bowel Disease. (2016)
  • Author(s): Fujii H, Shinzaki S, Iijima H, Wakamatsu K, Iwamoto C, Sobajima T, Kuwahara R, Hiyama S, Hayashi Y, Takamatsu S, Uozumi N, Kamada Y, Tsujii M, Taniguchi N, Takehara T, Miyoshi E
  • Journal Title: Gastroenterology Volume: 未定 Issue: 7 Pages: 00297-3
  • DOI: 10.1053/j.gastro.2016.03.002
  • NAID: 40021255019
  • Peer Reviewed
• [Journal Article] Role of aberrant IgG glycosylation in the pathogenesis of inflammatory bowel disease. (2016)
  • Author(s): Miyoshi E, Shinzaki S, Fujii H, Iijima H, Kamada Y, Takehara T.
  • Journal Title: Proteomics Clinical Applications Volume: 未定 Issue: 4 Pages: 384-390
  • DOI: 10.1002/prca.201500089
  • Peer Reviewed
• [Journal Article] Peyer's patches play a protective role in nonsteroidal anti-inflammatory drug-induced enteropathy in mice. (2014)
  • Author(s): Hiyama S, Iijima H, Shinzaki S, Inoue T, Shiraishi E, Kawai S, Araki M, Kato M, Hayashi Y, Nishida T, Fujii H, Mukai A, Shibata N, Sato S, Kiyono H, Gotoh K, Motooka D, Nakamura S, Iida T, Tsujii M, Takehara T.
  • Journal Title: Inflamm Bowel Dis. Volume: 5 Issue: 5 Pages: 790-9
  • DOI: 10.1097/mib.0000000000000017
  • Peer Reviewed / Open Access
• [Presentation] Age of onset is associated with disease seasonality in inflammatory bowel disease: A multi-center observational study by the Osaka Gut Forum (2016)
  • Author(s): Araki M, Shinzaki S, Iijima H, et al.
  • Organizer: 10th Congress of ECCO
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2016-02-18
  • Int'l Joint Research
• [Presentation] Deficiency of CCR7 Exacerbates Non-Steroidal Anti-Inflammatory Drug-Induced Enteropathy in Mice. (2016)
  • Author(s): Yamaguchi T, Iijima H, Hiyama S, Araki M, Kawai S, Iwatani S, Hayashi Y, Shinzaki S, Takehara T.
  • Organizer: Digestive Disease Week
  • Place of Presentation: San Diego, USA
  • Int'l Joint Research
• [Presentation] Indigo Naturalis and Indigo Ameliorate Murine Dextran Sodium Sulfate-Induced Colitis Through the Activation of Aryl Hydrocarbon Receptor. (2016)
  • Author(s): Kawai S, Iijima H, Shinzaki S, Iwatani S, Yamaguchi T, Araki M, Hiyama S, Hayashi Y, Tsujii M, Takehara T.
  • Organizer: Digestive Disease Week
  • Place of Presentation: San Diego, USA
  • Int'l Joint Research
• [Presentation] 潰瘍性大腸炎患者におけるパイエル板拡大観察の臨床的有用性 (2016)
  • Author(s): 日山智史, 飯島英樹, 新崎信一郎, 竹原徹郎
  • Organizer: 日本消化器病学会近畿支部 第105回例会
  • Place of Presentation: 大阪国際交流センター
• [Presentation] 青黛（indigo naturalis）による腸炎改善効果およびその機序についての検討 (2016)
  • Author(s): 川井 翔一朗, 飯島英樹, 竹原 徹郎
  • Organizer: 第102回日本消化器病学会総会
  • Place of Presentation: 京王プラザ
• [Presentation] マウスの NSAID 起因性小腸粘膜傷害におけるケモカインレセプター CCR7 の役割 (2016)
  • Author(s): 山口利朗, 飯島英樹, 日山智史, 良原丈夫, 岩谷修子, 荒木学, 川井翔一朗, 林義人, 新崎信一郎, 竹原徹郎
  • Organizer: 日本消化器免疫学会
  • Place of Presentation: 京都
• [Presentation] Biologics for mild to moderate UC, necessary (2015)
  • Author(s): Iijima H
  • Organizer: Annual Meeting of Asian Organization for Crohn's and Colitis,
  • Place of Presentation: Beijin, China
  • Year and Date: 2015-06-19
  • Int'l Joint Research / Invited
• [Presentation] Fujii H, Shinzaki S, Iijima H, et al. Core fucosylation regulates T-Cell activation and ameliorates murine colitis (2015)
  • Author(s): Fujii H, Shinzaki S, Iijima H, et al.
  • Organizer: Digestive Disease Week
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2015-05-16
  • Int'l Joint Research
• [Presentation] Age of onset is associated with seasonality of onset and exacerbation in inflammatory bowel disease: A multi-center observational study by the Osaka Gut Forum (2015)
  • Author(s): Araki M, Shinzaki S, Iijima H, et al.
  • Organizer: Digestive Disease Week
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2015-05-16
• [Presentation] パイエル板はNSAID起因性小腸粘膜傷害に保護的に働く (2014)
  • Author(s): 日山智史 ;飯島英樹 ;辻井正彦 ;竹原徹郎
  • Organizer: 日本消化器病学会近畿支部 第101回例会
  • Place of Presentation: 大阪国際交流センター
  • Year and Date: 2014-10-04
• [Presentation] Observation of Peyer's Patches Using Narrow Band Imaging With Magnifying Endoscopy Is Useful in Predicting the Recurrence of Ulcerative Colitis (2014)
  • Author(s): Satoshi Hiyama, Hideki Iijima, Shinichiro Shinzaki, et al.
  • Organizer: DDW
  • Place of Presentation: Chicago, USA
  • Year and Date: 2014-05-05 – 2014-05-06