High-endothelial cell-derived s1p regulates dendritic cell localization and vascular integrity in the lymph node

Simmons, Szandor; Sasaki, Naoko; Umemoto, Eiji; Uchida, Yutaka; Fukuhara, Shigetomo; Kitazawa, Yusuke; Okudaira, Michiyo; Inoue, Asuka; Tohya, Kazuo; Aoi, Keita; Aoki, Junken; Mochizuki, Naoki; Matsuno, Kenjiro; Takeda, Kiyoshi; Miyasaka, Masayuki; Ishii, Masaru

doi:https://doi.org/10.7554/eLife.41239

High-endothelial cell-derived s1p regulates dendritic cell localization and vascular integrity in the lymph node

Simmons, Szandor; Sasaki, Naoko; Umemoto, Eiji et al.

eLife, 2019, 8, e41239

Number of Access:2,134（2025-08-18 12:34 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/93171

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Title	High-endothelial cell-derived s1p regulates dendritic cell localization and vascular integrity in the lymph node
Creator	CreatorName Simmons, Szandor
	NRID 1000010388762 1000010388762 researchmap permalink sasaki_n sasaki_n CreatorName Sasaki, Naoko
	NRID 1000090452440 1000090452440 CreatorName Umemoto, Eiji
	NRID 1000050833787 1000050833787 researchmap permalink YutakaUchida YutakaUchida Scopus Author ID 56967526600 56967526600 CreatorName Uchida, Yutaka
	NRID 1000070332880 1000070332880 CreatorName Fukuhara, Shigetomo
	NRID 1000000467581 1000000467581 CreatorName Kitazawa, Yusuke
	CreatorName Okudaira, Michiyo
	NRID 1000050525813 1000050525813 CreatorName Inoue, Asuka
	NRID 1000090183491 1000090183491 CreatorName Tohya, Kazuo
	CreatorName Aoi, Keita
	NRID 1000020250219 1000020250219 CreatorName Aoki, Junken
	NRID 1000030311426 1000030311426 CreatorName Mochizuki, Naoki
	NRID 1000020094047 1000020094047 CreatorName Matsuno, Kenjiro
	NRID 1000020309446 1000020309446 ORCID 0000-0002-1778-6332 0000-0002-1778-6332 researchmap permalink read0118278 read0118278 Scopus Author ID 7404335442 7404335442 CreatorName Takeda, Kiyoshi
	NRID 1000050064613 1000050064613 CreatorName Miyasaka, Masayuki
	NRID 1000010324758 1000010324758 researchmap permalink read0076684 read0076684 Scopus Author ID 35074093500 35074093500 CreatorName Ishii, Masaru
Description	Simmons S., Sasaki N., Umemoto E., et al. High-endothelial cell-derived s1p regulates dendritic cell localization and vascular integrity in the lymph node. eLife 8, e41239 (2019); https://doi.org/10.7554/eLife.41239.
Abstract	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-Gi axis in HEVs, we generated Lyve1;Spns2Δ/Δ 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 Cdh5CRE-ERT2;S1pr1Δ/Δ 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-Gi signaling, and facilitates concomitant HEV-DC interactions.
Publisher	eLife Sciences Publications Ltd
Source Title	eLife
Volume (Issue)	8
Page	e41239
Date of Issued	2019-10-01
Language	English
Handle URL	https://hdl.handle.net/11094/93171
eISSN	2050084X
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.7554/eLife.41239
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	eLife. 2019, 8, p. e41239
DC.title	High-endothelial cell-derived s1p regulates dendritic cell localization and vascular integrity in the lymph node
DC.creator	Simmons, Szandor
	Sasaki, Naoko
	Umemoto, Eiji
	Uchida, Yutaka
	Fukuhara, Shigetomo
	Kitazawa, Yusuke
	Okudaira, Michiyo
	Inoue, Asuka
	Tohya, Kazuo
	Aoi, Keita
	Aoki, Junken
	Mochizuki, Naoki
	Matsuno, Kenjiro
	Takeda, Kiyoshi
	Miyasaka, Masayuki
	Ishii, Masaru
DC.publisher	eLife Sciences Publications Ltd
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2019-10-01
DC.identifier	https://doi.org/10.7554/eLife.41239
DC.description	Simmons S., Sasaki N., Umemoto E., et al. High-endothelial cell-derived s1p regulates dendritic cell localization and vascular integrity in the lymph node. eLife 8, e41239 (2019); https://doi.org/10.7554/eLife.41239.
DCTERMS.abstract	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-Gi axis in HEVs, we generated Lyve1;Spns2Δ/Δ 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 Cdh5CRE-ERT2;S1pr1Δ/Δ 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-Gi signaling, and facilitates concomitant HEV-DC interactions.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	93171
citation_title	High-endothelial cell-derived s1p regulates dendritic cell localization and vascular integrity in the lymph node
citation_author	Simmons, Szandor
	Sasaki, Naoko
	Umemoto, Eiji
	Uchida, Yutaka
	Fukuhara, Shigetomo
	Kitazawa, Yusuke
	Okudaira, Michiyo
	Inoue, Asuka
	Tohya, Kazuo
	Aoi, Keita
	Aoki, Junken
	Mochizuki, Naoki
	Matsuno, Kenjiro
	Takeda, Kiyoshi
	Miyasaka, Masayuki
	Ishii, Masaru
citation_publisher	eLife Sciences Publications Ltd
citation_language	English
citation_date	2019-10-01
citation_journal_title	eLife
citation_volume	8
citation_firstpage	e41239
citation_doi	https://doi.org/10.7554/eLife.41239
citation_public_url	https://hdl.handle.net/11094/93171

High-endothelial cell-derived s1p regulates dendritic cell localization and vascular integrity in the lymph node

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