Elucidation of molecular mechanism of cholera toxin-induced immune adjuvant effect

• Project/Area Number: 25870401
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology; Experimental pathology
• Research Institution: Wakayama Medical University (2014); Osaka University (2013)
• Principal Investigator: SASAKI Izumi 和歌山県立医科大学, 先端医学研究所, 助教 (80611037)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: コレラ毒素 / 樹状細胞

Outline of Final Research Achievements

Cholera toxin (CT) is well known as a strong mucosal adjuvant, which can induce IgA production and Th2 responses. However, the molecular basis how CT works as an immune adjuvant remains unknown. We have previously found that arginase I (ArgI) gene expression was strongly induced in CT-stimulated cells. Based on this phenomenon, we tried to clarify an elucidation of molecular mechanism of CT-induced immune adjuvant effect. First, we have performed screening of novel signaling molecules, which was involved in CT-induced immune adjuvant effect. Then, we have identified several molecules including PKA. Furthermore, we have clarified that PKA and ArgI were involved in CT plus LPS-induced synergistic IL-1β production at the post-transcriptional levels. We plan to further clarify the molecular mechanisms of CT-induced immune adjuvant effect.

Research Products

• [Journal Article] Transcription factor IRF8 plays a critical role in the development of murine basophils and mast cells. (2015)
  • Author(s): H. Sasaki, D. Kurotaki, N. Osato, H. Sato, I. Sasaki, S. Koizumi, H. Wang, C. Kaneda, A. Nishiyama, T. Kaisho, H. Aburatani, H. C. Morse III, K. Ozato, T. Tamura.
  • Journal Title: Blood Volume: 125(2) Issue: 2 Pages: 358-369
  • DOI: 10.1182/blood-2014-02-557983
  • Peer Reviewed / Open Access
• [Journal Article] Transcriptional Control of dendritic cell differentiation. (2014)
  • Author(s): I. Sasaki, T. Kaisho
  • Journal Title: Curr. Top. Microbiol. Immunol. Volume: 381 Pages: 257-278
  • DOI: 10.1007/82_2014_378
  • ISBN: 9783319073941, 9783319073958
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Limitation of immune tolerance-inducing thymic epithelial cell development by Spi-B-mediated negative feedback regulation. (2014)
  • Author(s): Akiyama, N., Shinzawa, M., Miyauchi, M., Yanai, H., Tateishi, R., Shimo, Y., Ohshima, D., Matsuo, M., Sasaki. I., Hoshino, K., Wu, G., Yagi, S., Inoue, J., Kaisho, T. and Akiyama, T.
  • Journal Title: J. Exp. Med. Volume: 211 Issue: 12 Pages: 2425-2438
  • DOI: 10.1084/jem.20141207
  • Peer Reviewed / Open Access
• [Journal Article] Critical roles of a dendritic cell subset expressing a chemokine receptor, XCR1 (2013)
  • Author(s): C. Yamazaki, M. Sugiyama, T. Ohta, H. Hemmi, E. Hamada, I. Sasaki, Y. Fukuda, T. Yano, M. Nobuoka, T. Hirashima, A. Iizuka, K. Sato, T. Tanaka, K. Hoshino, T. Kaisho
  • Journal Title: J. Immunol Volume: 190 Issue: 12 Pages: 6071-6082
  • DOI: 10.4049/jimmunol.1202798
  • Peer Reviewed
• [Presentation] Roles of Arginase I in Cholera toxin-induced production of proinflammatory cytokines (2014)
  • Author(s): Sasaki,I., Fukuda,S., Orimo,T., Hemmi,H., Kaisho,T.
  • Organizer: 第43回日本免疫学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] XCL1 and XCR1 are involved in intestinal immune homeostasis by dendritic cells (2014)
  • Author(s): Ohta,T., Okura,S., Hemmi,H., Sugiyama,M., Sasaki,I., Yamazaki,C., Hoshino,K., Kaisho,T.
  • Organizer: 第43回日本免疫学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] 腸管免疫制御機構におけるXCR1陽性樹状細胞の役割 (2014)
  • Author(s): 大田友和、邊見弘明、杉山正仲、佐々木泉、改正恒康
  • Organizer: 第24回 日本樹状細胞研究会
  • Place of Presentation: 山形
  • Year and Date: 2014-06-20
• [Presentation] 形質細胞様樹状細胞の機能と分化制御におけるEtsファミリー転写因子Spi-Bの役割 (2013)
  • Author(s): 佐々木 泉, 星野 克明, 辺見弘明, 改正恒康
  • Organizer: 第23回日本樹状細胞研究会
  • Place of Presentation: 国立京都国際会館
• [Presentation] The transcription factor IRF8 is required for basophil development (2013)
  • Author(s): SASAKI Haruka, KUROTAKI Daisuke, OSATO Naoki, SASAKI Izumi, KANEDA Chika, NISHIYAMA Akira, KAISHO Tsuneyasu, MORSE Herbert C. III, OZATO Keiko, TAMURA Tomohiko
  • Organizer: 第42回日本免疫学会総会
  • Place of Presentation: 幕張メッセ
• [Presentation] Anovel mechanism to generate the intestinal intraepithelial T lymphocytes by XCR1-expressing dendritic cells (2013)
  • Author(s): OHTA Tomokazu, HEMMI Hiroaki, YAMAZAKI Chihiro, SUGIYAMA Masanaka, SASAKi Izumi, HOSHINO Katsuaki, KAISHO Tsuneyasu
  • Organizer: 第42回日本免疫学会総会
  • Place of Presentation: 幕張メッセ
• [Presentation] Function of XCR1-expressing dendritic cells in oral tolerance (2013)
  • Author(s): HEMMI Hiroaki, SUGIYAMA Masanaka, OHTA Tomokazu, SASAKI Izumi, YAMAZAKI Chihiro, TANAKA Takashi, HOSHINO Katsuaki, KAISHO Tsuneyasu
  • Organizer: 第42回日本免疫学会総会
  • Place of Presentation: 幕張メッセ
• [Presentation] In vivo roles of XC chemokine receptor 1-expressing dendritic cells. (2013)
  • Author(s): Ohta T, Hemmi H, Yamazaki C, Sugiyama M, Sasaki I, Hoshino K, Kaisho T
  • Organizer: 15th International Congress of Immunology.
  • Place of Presentation: MiCo - Milano Congressi
• [Remarks] 和歌山県立医大 生体調節機構研究部 HP
  • URL: http://www.wakayama-med.ac.jp/med/seitai/
• [Remarks] 大阪大学免疫学フロンティア研究センター免疫機能統御学改正研究室
  • URL: http://immreg.ifrec.osaka-u.ac.jp/www/