Function of extracellular ADP-ribosyl cyclase BST-1/CD157 in the intestine

• Project/Area Number: 26460499
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Kawasaki Medical School
• Principal Investigator: Katsuhiko Ishihara 川崎医科大学, 医学部, 教授 (10263245)
• Co-Investigator(Kenkyū-buntansha): 矢作 綾野 川崎医科大学, 医学部, 助教 (10584873) ; 五十嵐 英哉 川崎医科大学, 医学部, 准教授 (40291538)
• Research Collaborator: HIRANO Hiroyasu 川崎医科大学, 医学部, 大学院生
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 腸内細菌叢 / 無菌マウス / ADPリボシルシクラーゼ / 腸管内常在細菌叢 / メタボローム解析 / 1型胸腺非依存性抗原 / 無菌化(germ free) / BST-1/CD157 / 腸内常在細菌叢 / ノックアウトマウス

Outline of Final Research Achievements

Bone marrow stromal cell antigen-1(BST-1)/CD157 is a GPI-anchored ectoenzyme having cyclase activity that converts NAD to cyclic ADP-ribose. BST-1 is now appreciated as an entero-neuro-immune regulator. Using the knock-out mice (KO) that lack CD157, CD38 or both, the functions of CD157 in the intestine was examined.The cells expressing CD157 or CD38 locate at distinct regions of the gut system.Decreased severity of DDS-induced colitis in CD157KO indicated that CD157 has a function to promote the colitis. Germ-free CD157KO exhibited the abnormal phenotypes in the cellular dynamics that had not been recognized in the SPF condition. T-RFLP analyses of the feces of double(D)KO revealed a reduced frequency of a certain Operational Taxonomic Unit in the microbiota compared with those of wild type mice. The metabolome analyses of the plasma of DKO revealed the changes in the amount of metabolites in the several pathways.
These data indicate that ADP-ribosyl cyclases regulates the microbiota.

Research Products

• [Int'l Joint Research] DNAX(米国)
• [Journal Article] An immunohistochemical, enzymatic, and behavioral study of CD157/BST-1 as a neuroregulator. (2017)
  • Author(s): Haruhiro Higashida, Mingkun Liang, Toru Yoshihara, Shirin Akther, Azam Fakhrul, Cherepanov Stanislav, Tae-Sik Nam, Uh-Hyun Kim, Satoka Kasai, Tomoko Nishimura, Naila Al Mahmuda, Shigeru Yokoyama, Katsuhiko Ishihara, Maria Gerasimenko, Alla Salmina, Jing Zhong, Takahiro Tsuji, Chiharu Tsuji and Olga Lopatina.
  • Journal Title: BMC Neuroscience Volume: 18 Issue: 1 Pages: 35-35
  • DOI: 10.1186/s12868-017-0350-7
  • NAID: 120006306237
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Lipo-oxytocin-1, A Novel Oxytocin Analog Conjugated with Two Palmitoyl Groups, Has Long-lasting Effects on Anxiety-related Behavior and Social Avoidance in CD157 Knockout Mice. (2015)
  • Author(s): A. Mizuno, S. M. Cherepanov, Y. Kikuchi, A. Fakhrul, S. Akther, K. Deguchi, T. Yoshihara, K. Ishihara, S. Shuto , H. Higashida
  • Journal Title: Brain Sci Volume: 5 Issue: 1 Pages: 3-13
  • DOI: 10.3390/brainsci5010003
  • Peer Reviewed
• [Journal Article] TNF receptor type 2 transmits caspase-dependent apoptotic signals in fibroblast-like synoviocytes derived from rheumatoid arthritis. (2015)
  • Author(s): Hiroyasu HIRANO, Hideya IGARASHI, Yoshitaka MORITA, Katsuhiko ISHIHARA
  • Journal Title: Kawasaki Medical Journal Volume: 41(2) Pages: 29-40
  • NAID: 110009986978
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Anxiety- and depression-like behavior in mice lacking the CD157/BST1 gene, a risk factor for Parkinson's disease. (2014)
  • Author(s): Lopatina O, Yoshihara T, Nishimura T, Zhong J, Akther S, Fakhrul AA, Liang M, Higashida C, Sumi K, Furuhara K, Inahata Y, Huang JJ, Koizumi K, Yokoyama S, Tsuji T, Petugina Y, Sumarokov A, Salmina AB, Hashida K, Kitao Y, Hori O, Asano M, Kitamura Y, Kozaka T, Shiba K, Zhong F, Xie MJ, Sato M, Ishihara K, Higashida H.
  • Journal Title: Front Behav Neurosci Volume: 8 Pages: 1-18
  • DOI: 10.3389/fnbeh.2014.00133
  • Peer Reviewed / Open Access
• [Journal Article] Infection-Immunity Liaison: Pathogen-driven autoimmune-mimicry (PDAIM) (2014)
  • Author(s): Saeki Y, Ishihara K
  • Journal Title: Autoimmunity Reviews Volume: 13 Issue: 10 Pages: 1064-9
  • DOI: 10.1016/j.autrev.2014.08.024
  • Peer Reviewed
• [Presentation] Lack of microbiota revealed the role for BST-1/CD157 to maintain the homeostasis at mucosa-MLN interface (2016)
  • Author(s): Katsuhiko ISHIHARA, Ayano YAHAGI, Takaaki NISHIMOTO, Masanori ISEKI
  • Organizer: 日本免疫学会
  • Place of Presentation: 沖縄コンベンションセンター(宜野湾市)
  • Year and Date: 2016-12-05
  • Int'l Joint Research
• [Presentation] Padi4 expression by neutrophils in the synovium appears in the earliest phase of arthritis in gp130F759 (2016)
  • Author(s): Ayano YAHAGI, Taro SAIKA, Katsuhiko ISHIHARA
  • Organizer: 日本免疫学会
  • Place of Presentation: 沖縄コンベンションセンター(宜野湾市)
  • Year and Date: 2016-12-05
  • Int'l Joint Research
• [Presentation] Eosinophils are not essential for pathological reactions in experimental allergic rhinitis, but suppress IgE production. (2016)
  • Author(s): Taro Saika, Ayano Yahagi, Katsuhiko Ishihara, Yukiyoshi Hyo, Tamotsu Harada
  • Organizer: 日本免疫学会
  • Place of Presentation: 沖縄コンベンションセンター(宜野湾市)
  • Year and Date: 2016-12-05
  • Int'l Joint Research
• [Presentation] Systemic infection with Mycoplasma fermentans facilitates development of arthritis in the knock-in mice gp130F759 through the action of neutrophils. (2016)
  • Author(s): Ayano YAHAGI, Hiroyasu HIRANO, Katsuhiko ISHIHARA
  • Organizer: 8th International forum on rheumatoid arthritis 2016
  • Place of Presentation: 品川プリンスホテル(東京)
  • Year and Date: 2016-10-21
  • Int'l Joint Research
• [Presentation] Mycoplasma fermentans感染により早期化するgp130F759の関節炎発症は好中球依存性である (2016)
  • Author(s): 矢作 綾野、石原 克彦
  • Organizer: 第27回日本生体防御学会
  • Place of Presentation: 九州大学病院キャンパスコラボステーションI(福岡市)
  • Year and Date: 2016-07-07
• [Presentation] Enhanced TI-1 antigen responses in BST-1/CD157 knock-out mice of C57BL/6J background. (2015)
  • Author(s): Katsuhiko Ishihara, Ayano Yahagi, Takaaki Nishimoto.
  • Organizer: 第44回日本免疫学会学術集会
  • Place of Presentation: 札幌コンベンションセンター(北海道・札幌市)
  • Year and Date: 2015-11-18
• [Presentation] Critical roles of neutrophils for development of arthritis in the knock-in mouse gp130F759 induced by systemic infection of Mycoplasma fermentans (2015)
  • Author(s): Ayano YAHAGI, Hiroyasu HIRANO, Hideya IGARASHI, Katsuhiko ISHIHARA
  • Organizer: 第44回日本免疫学会学術集会
  • Place of Presentation: 札幌コンベンションセンター(北海道・札幌市)
  • Year and Date: 2015-11-18
• [Remarks] 免疫学教室ホームページ
  • URL: http://www.kawasaki-m.ac.jp/med/study/info.php?id=208
• [Remarks] 免疫学教室ホームページ(英語版)
  • URL: http://www.kawasaki-m.ac.jp/med/en/research/basic_112.html