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

2015 Fiscal Year Final Research Report

• 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
• Keywords: Spns2 / S1P / HEV / Dendritic cells (DCs) / lymphocyte migration / CCL21

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.

Free Research Field

医歯薬学