GRK2-Dependent S1PR1 Desensitization Is Required for Lymphocytes to Overcome Their Attraction to Blood

Arnon, Tal I.; Xu, Ying; Lo, Charles G.; Pham, Trung H.M.; An, Jinping; Coughlin, Shaun R.; Dorn, Gerald W.; Cyster, Jason G.

doi:10.1126/science.1208248

Cited by 179 publications

(203 citation statements)

References 35 publications

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“…MZ B cells express the S1P receptors S1P 1 and S1P 3 highly, facilitating their S1P‐mediated attraction to the MZ 2, 3, 25. Continual S1P stimulation is required to retain MZ B cells in the MZ and it is the desensitization of S1P receptors on MZ B cells that enables them to overcome their attraction towards S1P in the blood30 and migrate into the follicles. Stromal cells, including FDC, within the B‐cell follicles express CXCL13,31 which stimulates the attraction of CXCR5‐expressing B cells towards the follicles 2, 3, 25, 32.…”

Section: Discussionmentioning

confidence: 99%

Ageing adversely affects the migration and function of marginal zone B cells

Turner

Mabbott

2017

Immunology

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SummaryMarginal zone (MZ) B cells are positioned within the spleen to capture blood‐borne antigen and immune complexes and deliver them to follicular dendritic cells in the B‐cell follicles. We show that within the spleens of aged mice antigen capture by MZ B cells, and their ability to shuttle between the follicle and MZ, were impaired. The ability of aged MZ B cells to migrate towards the MZ chemoattractant sphingosine‐1‐phosphate was increased, suggesting that aged MZ B cells had a greater propensity to be retained within the MZ. An extrinsic impairment in aged B‐cell migration towards the MZ was demonstrated using bone marrow chimeras. The follicular shuttling of MZ B cells derived from either young or aged bone marrow was similarly reduced in aged recipient spleens, showing that ageing effects on splenic stromal cells were responsible for the impaired follicular shuttling of MZ B cells. MZ B cells rapidly mount T‐cell‐independent (TI) antibody‐responses to microbial polysaccharide antigen. In aged mice the ability to produce immunoglobulins in response to the TI type 1 antigen TNP‐LPS was impaired. These ageing‐related changes to the MZ and MZ B cells have implications for the clearance of blood‐borne pathogens. Indeed elderly people have increased susceptibility to Streptococcus pneumoniae, a TI antigen, and decreased responses to vaccination. A thorough analysis of the mechanisms that underpin the ageing‐related decline in the status of the MZ and MZ B cells will help the design of novel treatments to improve immunity in the elderly.

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Section: Discussionmentioning

confidence: 99%

Ageing adversely affects the migration and function of marginal zone B cells

Turner

Mabbott

2017

Immunology

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“…Another gene involved in angiogenesis and endothelial cell differentiation is S1PR1 (sphingosine 1-phosphate receptor 1) which is one of the five G protein-coupled receptors for S1P1 (23). Previous studies have suggested that S1PR1 is required for stabilization of nascent blood vessels during embryonic development (24).…”

Section: Discussionmentioning

confidence: 99%

Genome-wide analysis of the effect of esophageal squamous cell carcinoma on human umbilical vein endothelial cells

et al. 2016

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Abstract.A large volume of data indicates that controlling tumor-associated angiogenesis is a promising therapy against cancer. However, angiogenesis is a complex process, little is known about the differential gene expression in the process of normal endothelial cell differentiation toward tumor vascular endothelial cells induced by tumor microenvironment. The aim of this study is to investigate the effect of tumor microenvironment simulated by the supernatant of esophageal squamous cancer cells (KYSE70) on normal endothelial cells (HUVECs) at the whole genome level. The gene expression profile was studied through gene ontology and signal pathway analysis. Compared with the normal HUVECs, a total of 3769 differentially expressed genes in induced HUVECs were detected, including 1609 upregulated genes and 2160 downregulated genes. Moreover, the microarray data analysis showed that 11 significant biological processes and 10 significant signaling pathways changed most, which are associated with angiogenesis and cell differentiation. According to the different expression levels in the microarrays and their functions, four differentially expressed genes involved in tumor angiogenesis and cell differentiation (IL6, VEGFA, S1PR1, TYMP) were selected and analyzed by qRT-PCR. The qRT-PCR results were consistent with the microarray data. Furthermore, we simulated the tumor microenvironment by human esophageal carcinoma tissue homogenate to investigate its effect on HUVECs, the qRT-PCR results indicated that the above genes were highly expressed in HUVECs after induction by esophageal carcinoma tissue homogenate. In conclusion, tumor microenvironment impact on normal endothelial cells differentiated toward tumor vascular endothelial cells, and the selected genes, which are associated with tumor angiogenesis, would be anti-angiogenesis targets against esophageal carcinoma.

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“…An S1P concentration gradient could in principle be created through secretion via S1P transporters such as Spinster2 [52], by HLMVEC-mediated depletion of S1P from the media, or both. S1P is a known chemoattractant for a variety of cell types [28,31,32,53,54]. Furthermore, activation of S1PR1 by S1P promotes lymphangiogenesis via Gai-dependent signalling [33].…”

Section: Cs-l15mentioning

confidence: 99%

“…The concentration of S1P is negligible in interstitial fluid, but is ca. 100 nM in blood and lymphatic fluid [28]. Because of this, the local concentration of S1P provides an important cue in the context of immunological function, lymphangiogenesis and blood vessel stabilization.…”

Section: Introductionmentioning

confidence: 99%

“…Because of this, the local concentration of S1P provides an important cue in the context of immunological function, lymphangiogenesis and blood vessel stabilization. Loss of S1PR1 in RBL-2H3 cells, derived from mast cells (a type of white blood cell), results in decreased chemotactic motility [29,30], and S1PR1 activation via S1P is required for lymphocyte egress from the thymus and secondary lymphoid organs in mice [28,31,32]. S1P promotes LEC sprouting in vitro in a manner that requires S1PR1 [33].…”

Section: Introductionmentioning

confidence: 99%

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Sphingosine 1-phosphate receptor 1 regulates the directional migration of lymphatic endothelial cells in response to fluid shear stress

Surya

Michalaki

Huang

et al. 2016

J. R. Soc. Interface.

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The endothelial cells that line blood and lymphatic vessels undergo complex, collective migration and rearrangement processes during embryonic development, and are known to be exquisitely responsive to fluid flow. At present, the molecular mechanisms by which endothelial cells sense fluid flow remain incompletely understood. Here, we report that both the G-protein-coupled receptor sphingosine 1-phosphate receptor 1 (S1PR1) and its ligand sphingosine 1-phosphate (S1P) are required for collective upstream migration of human lymphatic microvascular endothelial cells in an in vitro setting. These findings are consistent with a model in which signalling via S1P and S1PR1 are integral components in the response of lymphatic endothelial cells to the stimulus provided by fluid flow.

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GRK2-Dependent S1PR1 Desensitization Is Required for Lymphocytes to Overcome Their Attraction to Blood

Cited by 179 publications

References 35 publications

Ageing adversely affects the migration and function of marginal zone B cells

Ageing adversely affects the migration and function of marginal zone B cells

Genome-wide analysis of the effect of esophageal squamous cell carcinoma on human umbilical vein endothelial cells

Sphingosine 1-phosphate receptor 1 regulates the directional migration of lymphatic endothelial cells in response to fluid shear stress

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