CD4 T cell sphingosine 1-phosphate receptor (S1PR)1 and S1PR4 and endothelial S1PR2 regulate afferent lymphatic migration

Yanbao Xiong, Wenji Piao, C. Colin Brinkman, Lushen Li, Joseph M. Kulinski, Ana Olivera, Andreane Cartier, Timothy Hla, Keli L Hippen, Bruce R Blazar, Susan R. Schwab, Jonathan S. Bromberg

Research output: Contribution to journalArticle

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Abstract

Sphingosine 1-phosphate (S1P) and S1P receptors (S1PRs) regulate migration of lymphocytes out of thymus to blood and lymph nodes (LNs) to efferent lymph, whereas their role in other tissue sites is not known. Here, we investigated the question of how these molecules regulate leukocyte migration from tissues through afferent lymphatics to draining LNs (dLNs). S1P, but not other chemokines, selectively enhanced human and murine CD4 T cell migration across lymphatic endothelial cells (LECs). T cell S1PR1 and S1PR4, and LEC S1PR2, were required for migration across LECs and into lymphatic vessels and dLNs. S1PR1 and S1PR4 differentially regulated T cell motility and vascular cell adhesion molecule-1 (VCAM-1) binding. S1PR2 regulated LEC layer structure, permeability, and expression of the junction molecules VE-cadherin, occludin, and zonulin-1 through the ERK pathway. S1PR2 facilitated T cell transcellular migration through VCAM-1 expression and recruitment of T cells to LEC migration sites. These results demonstrated distinct roles for S1PRs in comodulating T cell and LEC functions in migration and suggest previously unknown levels of regulation of leukocytes and endothelial cells during homeostasis and immunity.

Original languageEnglish (US)
JournalScience Immunology
Volume4
Issue number33
DOIs
StatePublished - Mar 15 2019

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Lysosphingolipid Receptors
Endothelial Cells
T-Lymphocytes
Cell Movement
Vascular Cell Adhesion Molecule-1
Leukocytes
Lymph Nodes
Occludin
Lymphatic Vessels
MAP Kinase Signaling System
Lymph
Chemokines
Thymus Gland
Immunity
Permeability
Homeostasis
Lymphocytes

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Intramural
  • Research Support, N.I.H., Extramural

Cite this

CD4 T cell sphingosine 1-phosphate receptor (S1PR)1 and S1PR4 and endothelial S1PR2 regulate afferent lymphatic migration. / Xiong, Yanbao; Piao, Wenji; Brinkman, C. Colin; Li, Lushen; Kulinski, Joseph M.; Olivera, Ana; Cartier, Andreane; Hla, Timothy; Hippen, Keli L; Blazar, Bruce R; Schwab, Susan R.; Bromberg, Jonathan S.

In: Science Immunology, Vol. 4, No. 33, 15.03.2019.

Research output: Contribution to journalArticle

Xiong, Y, Piao, W, Brinkman, CC, Li, L, Kulinski, JM, Olivera, A, Cartier, A, Hla, T, Hippen, KL, Blazar, BR, Schwab, SR & Bromberg, JS 2019, 'CD4 T cell sphingosine 1-phosphate receptor (S1PR)1 and S1PR4 and endothelial S1PR2 regulate afferent lymphatic migration', Science Immunology, vol. 4, no. 33. https://doi.org/10.1126/sciimmunol.aav1263
Xiong, Yanbao ; Piao, Wenji ; Brinkman, C. Colin ; Li, Lushen ; Kulinski, Joseph M. ; Olivera, Ana ; Cartier, Andreane ; Hla, Timothy ; Hippen, Keli L ; Blazar, Bruce R ; Schwab, Susan R. ; Bromberg, Jonathan S. / CD4 T cell sphingosine 1-phosphate receptor (S1PR)1 and S1PR4 and endothelial S1PR2 regulate afferent lymphatic migration. In: Science Immunology. 2019 ; Vol. 4, No. 33.
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AU - Piao, Wenji

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AU - Li, Lushen

AU - Kulinski, Joseph M.

AU - Olivera, Ana

AU - Cartier, Andreane

AU - Hla, Timothy

AU - Hippen, Keli L

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AU - Bromberg, Jonathan S.

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