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

2019 ◽  
Vol 4 (33) ◽  
pp. eaav1263 ◽  
Author(s):  
Yanbao Xiong ◽  
Wenji Piao ◽  
C. Colin Brinkman ◽  
Lushen Li ◽  
Joseph M. Kulinski ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
T Cell ◽  
Layer Structure ◽  
Lymphatic Vessels ◽  
Cd4 T Cell ◽  
Lymphatic Endothelial Cells ◽  
T Cell Migration ◽  
Junction Molecules ◽  
Sphingosine 1 Phosphate ◽  
Cell Adhesion Molecule 1

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.

scholarly journals Macroautophagy in lymphatic endothelial cells inhibits T cell–mediated autoimmunity

2021 ◽  
Vol 218 (6) ◽  
Author(s):  
Guillaume Harlé ◽  
Camille Kowalski ◽  
Juan Dubrot ◽  
Dale Brighouse ◽  
Gaëlle Clavel ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Lymphatic Endothelial Cells ◽  
Inflammatory Conditions ◽  
Sphingosine 1 Phosphate ◽  
Tissue Antigens ◽  
Important Regulator ◽  
T Cell Survival

Lymphatic endothelial cells (LECs) present peripheral tissue antigens to induce T cell tolerance. In addition, LECs are the main source of sphingosine-1-phosphate (S1P), promoting naive T cell survival and effector T cell exit from lymph nodes (LNs). Autophagy is a physiological process essential for cellular homeostasis. We investigated whether autophagy in LECs modulates T cell activation in experimental arthritis. Whereas genetic abrogation of autophagy in LECs does not alter immune homeostasis, it induces alterations of the regulatory T cell (T reg cell) population in LNs from arthritic mice, which might be linked to MHCII-mediated antigen presentation by LECs. Furthermore, inflammation-induced autophagy in LECs promotes the degradation of Sphingosine kinase 1 (SphK1), resulting in decreased S1P production. Consequently, in arthritic mice lacking autophagy in LECs, pathogenic Th17 cell migration toward LEC-derived S1P gradients and egress from LNs are enhanced, as well as infiltration of inflamed joints, resulting in exacerbated arthritis. Our results highlight the autophagy pathway as an important regulator of LEC immunomodulatory functions in inflammatory conditions.

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

2016 ◽  
Vol 13 (125) ◽  
pp. 20160823 ◽  
Author(s):  
Vinay N. Surya ◽  
Eleftheria Michalaki ◽  
Eva Y. Huang ◽  
Gerald G. Fuller ◽  
Alexander R. Dunn
Keyword(s):  
Endothelial Cells ◽  
Fluid Flow ◽  
Molecular Mechanisms ◽  
Fluid Shear Stress ◽  
Lymphatic Vessels ◽  
Upstream Migration ◽  
Lymphatic Endothelial Cells ◽  
Sphingosine 1 Phosphate ◽  
G Protein Coupled

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.

scholarly journals GATA2 controls lymphatic endothelial cell junctional integrity and lymphovenous valve morphogenesis through miR-126

2019 ◽  
Author(s):  
Md. Riaj Mahamud ◽  
Xin Geng ◽  
Yen-Chun Ho ◽  
Boksik Cha ◽  
Yuenhee Kim ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Lymphatic Vessels ◽  
Lymphatic Endothelial Cell ◽  
Cell Junction ◽  
Lymphatic Endothelial Cells ◽  
Altered Expression ◽  
Junction Molecules ◽  
Lymphatic Valve ◽  
Oscillatory Shear Stress

ABSTRACTMutations in the transcription factor GATA2 cause lymphedema. GATA2 is necessary for the development of lymphatic valves (LVs) and lymphovenous valves (LVVs), and for the patterning of lymphatic vessels. Here, we report that GATA2 is not necessary for valvular endothelial cell (VEC) differentiation. Instead, GATA2 is required for VEC maintenance and morphogenesis. GATA2 is also necessary for the expression of cell junction molecules VE-Cadherin and Claudin5 in lymphatic vessels. We identified miR-126 as a target of GATA2, and miR-126−/− embryos recapitulate the phenotypes of mice lacking GATA2. Primary human lymphatic endothelial cells (HLECs) lacking GATA2 (GATA2ΔHLEC) have altered expression of Claudin5 and VE-Cadherin, and blocking miR-126 activity in HLECs phenocopies these changes in expression. Importantly, overexpression of miR-126 in GATA2ΔHLEC significantly rescues the cell junction defects. Thus, our work defines a new mechanism of GATA2 and uncovers miR-126 as a novel regulator of mammalian lymphatic vascular development.Non-standard abbreviationsLECs, lymphatic endothelial cells; LVs, lymphatic valves; LV-ECs, lymphatic valve-forming endothelial cells; LVVs, lymphovenous valves; LVV-ECs, lymphovenous valve-forming endothelial cells; HLEC, primary human LECs; OSS, Oscillatory shear stress; IHC, immunohistochemistry.

scholarly journals Roles of lymphatic endothelial cells expressing peripheral tissue antigens in CD4 T-cell tolerance induction

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Sherin J. Rouhani ◽  
Jacob D. Eccles ◽  
Priscila Riccardi ◽  
J. David Peske ◽  
Eric F. Tewalt ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
T Cell ◽  
Tolerance Induction ◽  
Peripheral Tissue ◽  
Cd4 T Cell ◽  
T Cell Tolerance ◽  
Cell Tolerance ◽  
Lymphatic Endothelial Cells ◽  
Tissue Antigens

scholarly journals IFNγ-Induced MHC Class II Expression on Islet Endothelial Cells Is an Early Marker of Insulitis but Is Not Required for Diabetogenic CD4+ T Cell Migration

2018 ◽  
Vol 9 ◽  
Author(s):  
Nicholas A. Scott ◽  
Yuxing Zhao ◽  
Balasubramanian Krishnamurthy ◽  
Stuart I. Mannering ◽  
Thomas W. H. Kay ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Migration ◽  
T Cell ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Cd4 T Cell ◽  
Early Marker ◽  
T Cell Migration

scholarly journals Human Brain Microvascular Endothelial Cells and Umbilical Vein Endothelial Cells Differentially Facilitate Leukocyte Recruitment and Utilize Chemokines for T Cell Migration

2008 ◽  
Vol 2008 ◽  
pp. 1-8 ◽  
Author(s):  
Shumei Man ◽  
Eroboghene E. Ubogu ◽  
Katherine A. Williams ◽  
Barbara Tucky ◽  
Melissa K. Callahan ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Migration ◽  
T Cell ◽  
Human Brain ◽  
Umbilical Vein ◽  
Microvascular Endothelial Cells ◽  
Brain Microvascular Endothelial Cells ◽  
T Cell Migration ◽  
Umbilical Vein Endothelial Cells

Endothelial cells that functionally express blood brain barrier (BBB) properties are useful surrogates for studying leukocyte-endothelial cell interactions at the BBB. In this study, we compared two different endothelial cellular models: transfected human brain microvascular endothelial cells (THBMECs) and human umbilical vein endothelial cells (HUVECs). With each grow under optimal conditions, confluent THBMEC cultures showed continuous occludin and ZO-1 immunoreactivity, while HUVEC cultures exhibited punctate ZO-1 expression at sites of cell-cell contact only. Confluent THBMEC cultures on 24-well collagen-coated transwell inserts had significantly higher transendothelial electrical resistance (TEER) and lower solute permeability than HUVECs. Confluent THBMECs were more restrictive for mononuclear cell migration than HUVECs. Only THBMECs utilized abluminal CCL5 to facilitate T-lymphocyte migration in vitro although both THBMECs and HUVECs employed CCL3 to facilitate T cell migration. These data establish baseline conditions for using THBMECs to develop in vitro BBB models for studying leukocyte-endothelial interactions during neuroinflammation.

scholarly journals Crosstalk between cancer cells and blood endothelial and lymphatic endothelial cells in tumour and organ microenvironment

2015 ◽  
Vol 17 ◽  
Author(s):  
Esak Lee ◽  
Niranjan B. Pandey ◽  
Aleksander S. Popel
Keyword(s):  
Endothelial Cells ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Tumour Growth ◽  
Tumour Progression ◽  
Lymphatic Vessels ◽  
Cell Types ◽  
Malignant Cell ◽  
Lymphatic Endothelial Cells ◽  
Tumour Blood

Tumour and organ microenvironments are crucial for cancer progression and metastasis. Crosstalk between multiple non-malignant cell types in the microenvironments and cancer cells promotes tumour growth and metastasis. Blood and lymphatic endothelial cells (BEC and LEC) are two of the components in the microenvironments. Tumour blood vessels (BV), comprising BEC, serve as conduits for blood supply into the tumour, and are important for tumour growth as well as haematogenous tumour dissemination. Lymphatic vessels (LV), comprising LEC, which are relatively leaky compared with BV, are essential for lymphogenous tumour dissemination. In addition to describing the conventional roles of the BV and LV, we also discuss newly emerging roles of these endothelial cells: their crosstalk with cancer cells via molecules secreted by the BEC and LEC (also called angiocrine and lymphangiocrine factors). This review suggests that BEC and LEC in various microenvironments can be orchestrators of tumour progression and proposes new mechanism-based strategies to discover new therapies to supplement conventional anti-angiogenic and anti-lymphangiogenic therapies.

scholarly journals Endothelin-1 Stimulates Lymphatic Endothelial Cells and Lymphatic Vessels to Grow and Invade

2009 ◽  
Vol 69 (6) ◽  
pp. 2669-2676 ◽  
Author(s):  
Francesca Spinella ◽  
Emirena Garrafa ◽  
Valeriana Di Castro ◽  
Laura Rosanò ◽  
Maria Rita Nicotra ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Lymphatic Vessels ◽  
Lymphatic Endothelial Cells ◽  
Endothelin 1
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