Impact of the active lipid-transporter Spinster-homologue-2 on S1P mediated immune cell dynamics

• Project/Area Number: 26860329
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Osaka University
• Principal Investigator: Simmons Szandor 大阪大学, 免疫学フロンティア研究センター, 特任助教(常勤) (60598176)
• Research Collaborator: Miyasaka Masayuki Osaka University ; Takeda Kiyoshi Osaka University ; Matsuno Kenjiro Dokkyo Medical University ; Mochizuki Naoki National Cerebral and Cardiovascular Center Research Institute ; Aoki Junken Tohoku University ; Tohya Kazuo Kansai University of Health Sciences ; Iida Tetsuya Osaka University
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: Spns2 / S1P / HEV / Dendritic cells (DCs) / lymphocyte migration / CCL21 / High endothelial venules / Dendritic Cells / DC / gut-immunity

Outline of Final Research Achievements

In order to reveal the role of the S1P-specific transporter Spinster-homologue-2 (Spns2) in controlling S1P-mediated lymphocyte egress into the lymphatic system we generated lymphatic endothelial cell-specific Spns2-KO mice. We detected a strong reduction of S1P in the lymph of KO mice, leading to the development of hypertrophic Peyer’s patches and hypotrophic lymph nodes (LNs). We could show that lymphocyte immigration into pLNs of KO mice in comparison to WT mice was significantly reduced. We detected severe impairment in morphology and size of high-endothelial venules (HEVs). We observed that DCs were absent in close proximity to the HEVs. Impaired micro-anatomical co-localization of DCs and HEVs in LNs was also observed if mice were treated with S1PR-antagonists. These studies reveal the importance of Spns2 to control S1P-driven lymphocyte egress and uncover new insights in the role of endothelial cell-derived S1P in controlling micro-anatomical migration of immune cells in LNs.

Research Products

• [Presentation] Implications of Spns2-deficiency on S1P-driven lymphocytes egress, HEV-integrity and immunity (2016)
  • Author(s): Szandor Simmons, Naoko Sasaki, Eiji Umemoto, Norie Yoshizumi, Shigetomo Fukuhara, Yusuke Kitazawa, Michiyo Okudaira, Asuka Inoue, Daisuke Motooka,Shota Nakamura,Tetsuya Iida, Kazuo Tohya, Junken Aoki, Naoki Mochizuki, Kenjiro Matsuno, Kiyoshi Takeda, Masayuki Miyasaka, Masaru Ishii
  • Organizer: The 16th International Congress of Immunology 2016, Melbourne, Australia
  • Place of Presentation: Mlebourne, Australia
  • Year and Date: 2016-08-21
• [Presentation] Implications of Spns2-deficiency on S1P-driven lymphocytes egress, HEV-integrity and immunity (2016)
  • Author(s): Szandor Simmons, Naoko Sasaki, Eiji Umemoto, Norie Yoshizumi, Shigetomo Fukuhara, Yusuke Kitazawa, Michiyo Okudaira, Asuka Inoue, Daisuke Motooka,Shota Nakamura,Tetsuya Iida, Kazuo Tohya, Junken Aoki, Naoki Mochizuki, Kenjiro Matsuno, Kiyoshi Takeda, Masayuki Miyasaka, Masaru Ishii
  • Organizer: 第2回日本骨免疫学会
  • Place of Presentation: Okinawa, Japan
  • Year and Date: 2016-07-06
• [Presentation] Spinster-homologue-2 (Spns2) controls S1P-driven lymphocyte egress from lymphoid organs (2015)
  • Author(s): Szandor Simmons, Naoko Sasaki, Eiji Umemoto, Norie Yoshizumi, Shigetomo Fukuhara, Yusuke Kitazawa, Michiyo Okudaira, Asuka Inoue, Daisuke Motooka,Shota Nakamura,Tetsuya Iida, Kazuo Tohya, Junken Aoki, Naoki Mochizuki, Kenjiro Matsuno, Kiyoshi Takeda, Masayuki Miyasaka, Masaru Ishii
  • Organizer: The 44th Annual Meeting of the Japanese Society for Immunology, Sapporo, Japan
  • Place of Presentation: Sapporo, Japan
  • Year and Date: 2015-11-18
  • Int'l Joint Research
• [Presentation] Spinster-homologue-2 (Spns2) controls S1P-driven lymphocyte egress from lymphoid organs (2015)
  • Author(s): Szandor Simmons
  • Organizer: Seminar series of the Max Planck Institute for Infection Biology, Berlin, Germany
  • Place of Presentation: Max Planck Institute for Infection Biology, Berlin, Germany
  • Year and Date: 2015-07-13
  • Invited
• [Presentation] Lymphocytes caught before the act – how Spinster-homologue-2 (Spns2) controls S1P-driven lymphocyte egress from lymphoid organs (2014)
  • Author(s): Szandor Simmons
  • Organizer: 43rd Annual Meeting of the Japanese Society for Immunology
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] Sphingosine-1-Phosphate: a Master Regulator of Osteoclast Precursor Migration, Lymphocyte Egress and Immunity (2014)
  • Author(s): Szandor Simmons
  • Organizer: International Symposium: "Imaging the inner life of cells"
  • Place of Presentation: Osaka, Japan
  • Year and Date: 2014-11-21
  • Invited
• [Presentation] Lymphocytes caught before the act – how Spinster-homologue-2 (Spns2) controls S1P-driven lymphocyte egress from lymphoid organs (2014)
  • Author(s): Szandor Simmons
  • Organizer: 44th Annual Meeting of the German Society for Immunology
  • Place of Presentation: Bonn, Germany
  • Year and Date: 2014-09-17 – 2014-09-20