Novel regulatory mechanisms of the intestinal immunity via the microvilli of intestinal epithelial cells

• Project/Area Number: 16K15219
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Kobe University
• Principal Investigator: Matozaki Takashi 神戸大学, 医学研究科, 教授 (80252782)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 腸上皮細胞 / 微絨毛 / 腸管免疫 / チロシンホスファターゼ / 腸内細菌

Outline of Final Research Achievements

SAP-1, a receptor-type protein tyrosine phosphatase that is specifically expressed in intestinal epithelial cells, likely participates in the regulation of intestinal immunity by controlling the tyrosine phosphorylation level of its ligand CEACAM20. In this study, the regulatory mechanisms of SAP-1/CEACAM20-function and -expression were analyzed in vitro and in vivo. I showed a part of regulatory mechanisms of SAP-1/CEACAM20-mediated intestinal immunity.

Research Products

• [Journal Article] Regulation by commensal bacteria of neurogenesis in the subventricular zone of adult mouse brain (2018)
  • Author(s): Sawada Naoki、Kotani Takenori、Konno Tasuku、Setiawan Jajar、Nishigaito Yuka、Saito Yasuyuki、Murata Yoji、Nibu Ken-ichi、Matozaki Takashi
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 498 Issue: 4 Pages: 824-829
  • DOI: 10.1016/j.bbrc.2018.03.064
  • NAID: 120006733123
  • Peer Reviewed
• [Journal Article] Anti-human SIRPα antibody is a new tool for cancer immunotherapy (2018)
  • Author(s): Murata Yoji、Tanaka Daisuke、Hazama Daisuke、Yanagita Tadahiko、Saito Yasuyuki、Kotani Takenori、Oldenborg Per-Arne、Matozaki Takashi
  • Journal Title: Cancer Science Volume: 印刷中 Issue: 5 Pages: 1300-1308
  • DOI: 10.1111/cas.13548
  • NAID: 120006482611
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Microvillus-specific protein tyrosine phosphatase SAP-1 plays a role in regulating the intestinal paracellular transport of macromolecules. (2017)
  • Author(s): Mori S, Kamei N, Murata Y, Takayama K, Matozaki T, Takeda-Morishita M.
  • Journal Title: J Pharm Sci. Volume: 106 Issue: 9 Pages: 2904-2908
  • DOI: 10.1016/j.xphs.2017.04.014
  • Peer Reviewed
• [Journal Article] Human and murine splenic neutrophils are potent phagocytes of IgG-opsonized red blood cells (2017)
  • Author(s): Meinderts Sanne M.、Oldenborg Per-Arne、Beuger Boukje M.、Klei Thomas R. L.、Johansson Johanna、Kuijpers Taco W.、Matozaki Takashi、Huisman Elise J.、de Haas Masja、van den Berg Timo K.、van Bruggen Robin
  • Journal Title: Blood Advances Volume: 1 Issue: 14 Pages: 875-886
  • DOI: 10.1182/bloodadvances.2017004671
  • NAID: 120006377653
  • Peer Reviewed
• [Journal Article] SIRPα+dendritic cells regulate homeostasis of fibroblastic reticular cells via TNF receptor ligands in the adult spleen (2017)
  • Author(s): Saito Yasuyuki、Respatika Datu、Komori Satomi、Washio Ken、Nishimura Taichi、Kotani Takenori、Murata Yoji、Okazawa Hideki、Ohnishi Hiroshi、Kaneko Yoriaki、Yui Katsuyuki、Yasutomo Koji、Nishigori Chikako、Nojima Yoshihisa、Matozaki Takashi
  • Journal Title: Proceedings of the National Academy of Sciences Volume: 114 Issue: 47
  • DOI: 10.1073/pnas.1711345114
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Donor SIRPα polymorphism modulates the innate immune response to allogeneic grafts (2017)
  • Author(s): Dai Hehua、Friday Andrew J.、Abou-Daya Khodor I.、Williams Amanda L.、Mortin-Toth Steven、Nicotra Matthew L.、Rothstein David M.、Shlomchik Warren D.、Matozaki Takashi、Isenberg Jeffrey S.、Oberbarnscheidt Martin H.、Danska Jayne S.、Lakkis Fadi G.
  • Journal Title: Science Immunology Volume: 2 Issue: 12
  • DOI: 10.1126/sciimmunol.aam6202
  • Peer Reviewed
• [Journal Article] Prion pathogenesis is unaltered in the absence of SIRPα-mediated "don't-eat-me" signaling (2017)
  • Author(s): Nuvolone Mario、Paolucci Marta、Sorce Silvia、Kana Veronika、Moos Rita、Matozaki Takashi、Aguzzi Adriano
  • Journal Title: PLOS ONE Volume: 12 Issue: 5 Pages: e0177876-e0177876
  • DOI: 10.1371/journal.pone.0177876
  • NAID: 120006373778
  • Peer Reviewed
• [Journal Article] Promotion of intestinal epithelial cell turnover by commensal bacteria: role of short-chain fatty acids. (2016)
  • Author(s): Park J.H., Kotani T., Konno T., Setiawan J., Kitamura Y., Imada S., Usui Y., Hatano N., Shinohara M., Saito Y., Murata Y., and Matozaki T.
  • Journal Title: PloS One Volume: 11 Issue: 5 Pages: e0156334-e0156334
  • DOI: 10.1371/journal.pone.0156334
  • NAID: 120005774020
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Role of Src family kinases in regulation of intestinal epithelial homeostasis. (2016)
  • Author(s): Imada S, Murata Y, Kotani T, Hatano M, Sun C, Konno T, Park JH, Kitamura Y, Saito Y, Ohdan H, Matozaki T.
  • Journal Title: Mol Cell Biol Volume: 36 Issue: 22 Pages: 2811-2823
  • DOI: 10.1128/mcb.00311-16
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Future therapeutic potential of SAP-1 in inflammatory bowel diseases (2016)
  • Author(s): Kotani T, Murata Y, Saito Y, Matozaki T.
  • Journal Title: Expert Rev Gastroenterol Hepatol. Volume: 10 Issue: 12 Pages: 1313-1315
  • DOI: 10.1080/17474124.2016.1245144
  • Peer Reviewed
• [Presentation] Regulation of intestinal immunity by the microvillus-specific protein tyrosine phosphatase SAP-1 and its substrate CEACAM20 (2017)
  • Author(s): Takenori Kotani, Yoji Murata, Yana Supriatna, Yasuaki Kitamura, Shinya Imada, Yasuyuki Saito, Hideki Okazawa, Hiroshi Ohnishi, Takashi Matozaki
  • Organizer: Europhosphatase 2019:Phosphatases in cell fates and decisions
  • Int'l Joint Research
• [Presentation] Short chain fatty acids regulate the turnover of intestinal epithelial cells (2016)
  • Author(s): 金野 祐、小谷 武徳、朴 貞河、Jajar Setiawan、北村 泰明、今田 慎也、臼井 佑太郎、波多野 直哉、篠原 正和、齊藤 泰之、村田 陽二、的崎 尚
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 仙台国際センター
  • Year and Date: 2016-09-25
• [Presentation] 受容体型チロシンホスファターゼSAP-1による腸管免疫制御 (2016)
  • Author(s): 村田 陽二、小谷 武徳、齊藤 泰之、的崎 尚
  • Organizer: 第15回生体機能研究会
  • Place of Presentation: 淡路夢舞台国際会議場
  • Year and Date: 2016-07-01
• [Presentation] 成熟細胞の寿命制御とその破綻による病態に関する研究-腸上皮細胞をモデルとして- (2016)
  • Author(s): 的崎 尚
  • Organizer: 第47回広島消化管疾患研究会
  • Place of Presentation: ホテルグランヴィア広島
  • Invited
• [Remarks] 神戸大学大学院医学研究科生化学・分子生物学講座シグナル統合学分野
  • URL: http://www.med.kobe-u.ac.jp/tougou/signal/Home.html
• [Remarks] 神戸大学大学院医学研究科 生化学・分子生物学講座 シグナル統合学分野
  • URL: http://www.med.kobe-u.ac.jp/tougou/signal/Home.html