PMID- 31570118
OWN - NLM
STAT- MEDLINE
DCOM- 20200211
LR  - 20200211
IS  - 2050-084X (Electronic)
IS  - 2050-084X (Linking)
VI  - 8
DP  - 2019 Oct 1
TI  - High-endothelial cell-derived S1P regulates dendritic cell localization and 
      vascular integrity in the lymph node.
LID - 10.7554/eLife.41239 [doi]
LID - e41239
AB  - While the sphingosine-1-phosphate (S1P)/sphingosine-1-phosphate receptor-1 
      (S1PR1) axis is critically important for lymphocyte egress from lymphoid organs, 
      S1PR1-activation also occurs in vascular endothelial cells (ECs), including those 
      of the high-endothelial venules (HEVs) that mediate lymphocyte immigration into 
      lymph nodes (LNs). To understand the functional significance of the 
      S1P/S1PR1-G(i) axis in HEVs, we generated Lyve1;Spns2(Delta/Delta) conditional knockout 
      mice for the S1P-transporter Spinster-homologue-2 (SPNS2), as HEVs express LYVE1 
      during development. In these mice HEVs appeared apoptotic and were severely 
      impaired in function, morphology and size; leading to markedly hypotrophic 
      peripheral LNs. Dendritic cells (DCs) were unable to interact with HEVs, which 
      was also observed in Cdh5(CRE-ERT2);S1pr1(Delta/Delta) mice and wildtype mice treated 
      with S1PR1-antagonists. Wildtype HEVs treated with S1PR1-antagonists in vitro and 
      Lyve1-deficient HEVs show severely reduced release of the DC-chemoattractant 
      CCL21 in vivo. Together, our results reveal that EC-derived S1P warrants 
      HEV-integrity through autocrine control of S1PR1-G(i) signaling, and facilitates 
      concomitant HEV-DC interactions.
CI  - (c) 2019, Simmons et al.
FAU - Simmons, Szandor
AU  - Simmons S
AUID- ORCID: 0000-0001-9619-0942
AD  - Department of Immunology and Cell Biology, Graduate School of Medicine and 
      Frontier Biosciences, Osaka University, Osaka, Japan.
AD  - WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.
AD  - JST CREST, Tokyo, Japan.
FAU - Sasaki, Naoko
AU  - Sasaki N
AD  - Department of Microbiology and Immunology, Laboratory of Immune Regulation, 
      Graduate School of Medicine, Osaka University, Osaka, Japan.
FAU - Umemoto, Eiji
AU  - Umemoto E
AD  - WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.
AD  - Department of Microbiology and Immunology, Laboratory of Immune Regulation, 
      Graduate School of Medicine, Osaka University, Osaka, Japan.
FAU - Uchida, Yutaka
AU  - Uchida Y
AD  - Department of Immunology and Cell Biology, Graduate School of Medicine and 
      Frontier Biosciences, Osaka University, Osaka, Japan.
AD  - JST CREST, Tokyo, Japan.
FAU - Fukuhara, Shigetomo
AU  - Fukuhara S
AD  - Department of Cell Biology, National Cerebral and Cardiovascular Center Research 
      Institute, Osaka, Japan.
FAU - Kitazawa, Yusuke
AU  - Kitazawa Y
AD  - Department of Anatomy (Macro), Dokkyo Medical University, Tochigi, Japan.
FAU - Okudaira, Michiyo
AU  - Okudaira M
AD  - Laboratory of Molecular and Cellular Biochemistry, Graduate School of 
      Pharmaceutical Sciences, Tohoku University, Miyagi, Japan.
FAU - Inoue, Asuka
AU  - Inoue A
AD  - Laboratory of Molecular and Cellular Biochemistry, Graduate School of 
      Pharmaceutical Sciences, Tohoku University, Miyagi, Japan.
FAU - Tohya, Kazuo
AU  - Tohya K
AD  - Department of Anatomy, Kansai University of Health Sciences, Osaka, Japan.
FAU - Aoi, Keita
AU  - Aoi K
AD  - Department of Immunology and Cell Biology, Graduate School of Medicine and 
      Frontier Biosciences, Osaka University, Osaka, Japan.
AD  - WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.
AD  - JST CREST, Tokyo, Japan.
FAU - Aoki, Junken
AU  - Aoki J
AD  - Laboratory of Molecular and Cellular Biochemistry, Graduate School of 
      Pharmaceutical Sciences, Tohoku University, Miyagi, Japan.
FAU - Mochizuki, Naoki
AU  - Mochizuki N
AUID- ORCID: 0000-0002-3938-9602
AD  - Department of Cell Biology, National Cerebral and Cardiovascular Center Research 
      Institute, Osaka, Japan.
FAU - Matsuno, Kenjiro
AU  - Matsuno K
AD  - Department of Anatomy (Macro), Dokkyo Medical University, Tochigi, Japan.
FAU - Takeda, Kiyoshi
AU  - Takeda K
AD  - WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.
AD  - Department of Microbiology and Immunology, Laboratory of Immune Regulation, 
      Graduate School of Medicine, Osaka University, Osaka, Japan.
FAU - Miyasaka, Masayuki
AU  - Miyasaka M
AD  - WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.
AD  - MediCity Research Laboratory, University of Turku, Turku, Finland.
AD  - Interdisciplinary Program for Biomedical Sciences, Institute for Academic 
      Initiatives, Osaka University, Osaka, Japan.
FAU - Ishii, Masaru
AU  - Ishii M
AD  - Department of Immunology and Cell Biology, Graduate School of Medicine and 
      Frontier Biosciences, Osaka University, Osaka, Japan.
AD  - WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.
AD  - JST CREST, Tokyo, Japan.
LA  - eng
GR  - Grants-in-Aid for Scientific Research (A) JP25253070/Japan Society for the 
      Promotion of Science/International
GR  - Research Grant/Takeda Science Foundation/International
GR  - Research Grant/Kanae Foundation for the Promotion of Medical 
      Science/International
GR  - Research Grant/Uehara Memorial Foundation/International
GR  - Grants-in-Aid for Young Scientists (B) JP26860329/Japan Society for the Promotion 
      of Science/International
GR  - Postdoctoral Fellowship/Kishimoto Foundation/International
GR  - Grants-in-Aid for Scientific Research (A) JP16H02619/Japan Society for the 
      Promotion of Science/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191001
PL  - England
TA  - Elife
JT  - eLife
JID - 101579614
RN  - 0 (Lysophospholipids)
RN  - 0 (S1pr1 protein, mouse)
RN  - 0 (Sphingosine-1-Phosphate Receptors)
RN  - 26993-30-6 (sphingosine 1-phosphate)
RN  - NGZ37HRE42 (Sphingosine)
SB  - IM
MH  - Animals
MH  - *Cell Movement
MH  - Dendritic Cells/*physiology
MH  - Endothelial Cells/*physiology
MH  - Lymph Nodes/*cytology
MH  - Lysophospholipids/*metabolism
MH  - Mice, Knockout
MH  - Sphingosine/*analogs & derivatives/metabolism
MH  - Sphingosine-1-Phosphate Receptors/*metabolism
PMC - PMC6773441
OTO - NOTNLM
OT  - Spinster-homologue-2
OT  - apopotosis
OT  - dendritic cells
OT  - high-endothelial venules
OT  - immunology
OT  - inflammation
OT  - lymphocyte migration
OT  - mouse
OT  - sphingosine-1-phosphate
COIS- SS, NS, EU, YU, SF, YK, MO, AI, KT, KA, JA, NM, KM, KT, MM, MI No competing 
      interests declared
EDAT- 2019/10/02 06:00
MHDA- 2020/02/12 06:00
PMCR- 2019/10/01
CRDT- 2019/10/02 06:00
PHST- 2018/08/19 00:00 [received]
PHST- 2019/09/10 00:00 [accepted]
PHST- 2019/10/02 06:00 [entrez]
PHST- 2019/10/02 06:00 [pubmed]
PHST- 2020/02/12 06:00 [medline]
PHST- 2019/10/01 00:00 [pmc-release]
AID - 41239 [pii]
AID - 10.7554/eLife.41239 [doi]
PST - epublish
SO  - Elife. 2019 Oct 1;8:e41239. doi: 10.7554/eLife.41239.