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

アクセス数:152件（2025-04-08 02:04 集計）

固定URL: https://hdl.handle.net/11094/93171

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タイトル	High-endothelial cell-derived s1p regulates dendritic cell localization and vascular integrity in the lymph node
著者	著者名 Simmons, Szandor
	NRID 1000010388762 1000010388762 researchmap permalink sasaki_n sasaki_n 著者名 Sasaki, Naoko
	NRID 1000090452440 1000090452440 著者名 Umemoto, Eiji
	NRID 1000050833787 1000050833787 researchmap permalink YutakaUchida YutakaUchida Scopus Author ID 56967526600 56967526600 著者名 Uchida, Yutaka
	NRID 1000070332880 1000070332880 著者名 Fukuhara, Shigetomo
	NRID 1000000467581 1000000467581 著者名 Kitazawa, Yusuke
	著者名 Okudaira, Michiyo
	NRID 1000050525813 1000050525813 著者名 Inoue, Asuka
	NRID 1000090183491 1000090183491 著者名 Tohya, Kazuo
	著者名 Aoi, Keita
	NRID 1000020250219 1000020250219 著者名 Aoki, Junken
	NRID 1000030311426 1000030311426 著者名 Mochizuki, Naoki
	NRID 1000020094047 1000020094047 著者名 Matsuno, Kenjiro
	NRID 1000020309446 1000020309446 ORCID 0000-0002-1778-6332 0000-0002-1778-6332 researchmap permalink read0118278 read0118278 Scopus Author ID 7404335442 7404335442 著者名 Takeda, Kiyoshi
	NRID 1000050064613 1000050064613 著者名 Miyasaka, Masayuki
	NRID 1000010324758 1000010324758 researchmap permalink read0076684 read0076684 Scopus Author ID 35074093500 35074093500 著者名 Ishii, Masaru
内容	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.
抄録	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.
出版者	eLife Sciences Publications Ltd
収録物名	eLife
巻(号)	8
ページ	e41239
刊行年月	2019-10-01
言語	英語
ハンドルURL	https://hdl.handle.net/11094/93171
eISSN	2050084X
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.7554/eLife.41239
アクセス権	open access
権利情報	This article is licensed under a Creative Commons Attribution 4.0 International License.
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCMI資源タイプ	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	英語
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	英語
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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