2015 Fiscal Year Annual Research Report
Impact of the active lipid-transporter Spinster-homoloque-2 on S1P-mediated immune cell dynamics
| Project/Area Number |
26860329
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| Research Institution | Osaka University |
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Principal Investigator |
シモンス シャンドゥア 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)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Keywords | Spns2 / High endothelial venules / HEV / Dendritic Cells / DC / CCL21 |
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| Outline of Annual Research Achievements |
Recent studies emphasized an essential role of S1P in the regulation of endothelial cell function its influence on preserving high-endothelial cell integrity remains elusive. We focus special attention on the S1P-transporter Spinster-homologue-2 (Spns2), and the secretion of S1P by Lyve1+ lymphatic endothelial cells (LECs) and high-endothelial cells. We detected strong reduction of S1P in the lymph of conditional Lyve1-Spns2Δ/Δ (KO) mice. Interestingly, dendritic cells (DCs) were unable to interact with high-endothelial venules (HEVs) in peripheral lymph nodes (pLNs) of KO mice. Hence, DCs were unable to provide angiogenic factors like lymphotoxin-β for regular development and function of HEVs. Importantly, we detected severe impairment in function, morphology and size of HEVs in pLNs of KO mice. Consequently, we observed impaired immigration of lymphocytes resulting in the development of hypotrophic LNs. Impaired co-localization of DCs and HEVs in LNs was also observed if mice were treated with S1PR1-antagonists. Furthermore, S1PR1-Gi signaling was reduced in HEVs of KO mice. In addition, release of the DC-chemoattractant CCL21 was reduced from HEVs in KO mice. Together, our results reveal a previously unsuspected role of endothelial cell-derived S1P in maintaining HEV-integrity by facilitating DC and HEV interactions through the control of S1PR1-dependent HEV-specific CCL21-secretion. These findings give new insights into the S1P-mediated autocrine regulation of chemokine responses of HEVs as well as the regulation of lymphocyte recirculation during immune surveillance
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Research Products
(4 results)
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[Presentation] Implications of Spns2-deficiency on S1P-driven lymphocytes egress, HEV-integrity and immunity2016
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 – 2016-08-26
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[Presentation] Implications of Spns2-deficiency on S1P-driven lymphocytes egress, HEV-integrity and immunity2016
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 – 2016-07-08
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[Presentation] Spinster-homologue-2 (Spns2) controls S1P-driven lymphocyte egress from lymphoid organs2015
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 – 2015-11-20
Int'l Joint Research
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