Molecular association of Death receptor 6 with peripheral lymphocyte activation

• Project/Area Number: 25870017
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry; Experimental pathology
• Research Institution: Hokkaido University
• Principal Investigator: Fujikura Daisuke 北海道大学, 人獣共通感染症リサーチセンター, 特任助教 (70547794)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: death receptor 6 / T細胞 / DR6

Outline of Final Research Achievements

Activation of peripheral lymphocytes is a critical step for host protection against infections and tumors. Since ‘high’ activation of the cells induces severe systemic immunological disorders, the activation should be accurately regulated. The regulation depends on the association between several surface molecules that are expressed on the cells. Death receptor 6 (DR6) is an orphan receptor that expresses on peripheral T lymphocytes. However, the detail of the molecule remains unclear. Here, we generated a novel anti-DR6 specific antibody that has an activity for the receptor cross-linking. Using this antibody, we found the induction of DR6 expressing T cells in the disease progression of systemic lupus erythematosus animal model. Administration of the antibody suppressed the activation of T cells. Importantly, the administration also delayed the disease progression of the animal model. These findings indicate that DR6 might be a novel therapeutic target for immunological disorders.

Research Products

• [Journal Article] The Interaction between TIM-1 and NPC1 is important for the cellular entry of Ebola virus (2015)
  • Author(s): Kuroda M, Fujikura D, Nanbo A, Marzi A, Noyori O, Kajihara M, Maruyama J, Matsuno K, Miyamoto H, Yoshida R, Feldmann H, Takada A
  • Journal Title: J. Virol. Volume: 印刷中 Issue: 12 Pages: 6481-6493
  • DOI: 10.1128/jvi.03156-14
  • NAID: 120005621883
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] <i>Bacillus cereus</i> from the environment is genetically related to the highly pathogenic <i>B. cereus</i> in Zambia (2015)
  • Author(s): Ogawa H, Ohnuma M, Squarre D, Mweene AS, Ezaki T, Fujikura D, Ohnishi N, Thomas Y, Hang'ombe BM, Higashi H.
  • Journal Title: Journal of Veterinary Medical Science Volume: 77 Issue: 8 Pages: 993-995
  • DOI: 10.1292/jvms.15-0059
  • NAID: 130005094678
  • ISSN: 0916-7250, 1347-7439
  • Peer Reviewed / Open Access
• [Journal Article] A novel multiplex PCR discriminates Bacillus anthracis and its genetically related strains from other Bacillus cereus group species (2015)
  • Author(s): Ogawa H., Fujikura D., Ohnuma M., Ohnishi N., Hang'ombe B.M., Mimuro M., Ezaki T., Mweene A.S., Higashi H
  • Journal Title: PLoS One Volume: 10 Issue: 3 Pages: e0122004-e0122004
  • DOI: 10.1371/journal.pone.0122004
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A polymorphism of the TIM-1 IgV domain: Implications for the susceptibility to filovirus infection. (2014)
  • Author(s): Makoto Kuroda, Daisuke Fujikura, Osamu Noyori, Masahiro Kajihara, Junki Maruyama, Hiroko Miyamoto, Reiko Yoshida, Ayato Takada.
  • Journal Title: Biochemical and biophysical research communications Volume: 455 Issue: 3-4 Pages: 223-228
  • DOI: 10.1016/j.bbrc.2014.10.144
  • Peer Reviewed / Open Access
• [Journal Article] Genome Sequence of a Bacillus anthracis Outbreak Strain from Zambia, 2011. (2014)
  • Author(s): Ohnishi N, Maruyama F, Ogawa H, Kachi H, Yamada S, Fujikura D, Nakagawa I, Hang'ombe MB, Thomas Y, Mweene AS, Higashi H.
  • Journal Title: Genome Announc. Volume: 2(2)
  • Peer Reviewed
• [Journal Article] Heat Shock Protein 70 Modulates Influenza A Virus Polymerase Activity (2013)
  • Author(s): Manzoor R, Kuroda K, Yoshida R, Tsuda Y, Fujikura D, Miyamoto H, Kajihara M, Kida H, Takada A
  • Journal Title: J. Biol. Chem. Volume: 289 Issue: 11 Pages: 7599-7614
  • DOI: 10.1074/jbc.m113.507798
  • NAID: 120005460233
  • Peer Reviewed
• [Presentation] Death receptor 6 is involved in a regulatory mechanism for follicular helper T cell. (2015)
  • Author(s): Daisuke FUJIKURA
  • Organizer: The 14th Awaji International Forum on Infection and Immunity, September 8-11, 2015 Awaji Oral and Poster presentation
  • Place of Presentation: Awaji Yumebutai International Conference Center, Awaji, Hyogo, Japan
  • Year and Date: 2015-09-08
  • Int'l Joint Research
• [Presentation] Development of a Novel Anthrax Vaccine Antigen and Analysis of Molecular Pathogenicity in Bacillus anthracis Infection. (2014)
  • Author(s): Daisuke FUJIKURA, Memi Mutoh, Naomi Ohnishi, Miyuki Ohnuma, Hirohito Ogawa, Bernard M. Hang’Ombe, Aaron S. Mweene and Hideaki Higashi
  • Organizer: Asian-African Research Forum on Emerging and Reemerging Infections 2014
  • Place of Presentation: Sendai international center, sendai, Japan
• [Patent(Industrial Property Rights)] 免疫制御剤 (2013)
  • Inventor(s): 藤倉大輔、上出利光
  • Industrial Property Rights Holder: 藤倉大輔、上出利光
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-11-20