scholarly journals Single-Cell Transcriptional Heterogeneity of Lymphatic Endothelial Cells in Normal and Inflamed Murine Lymph Nodes

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1371
Author(s):  
Eliane Sibler ◽  
Yuliang He ◽  
Luca Ducoli ◽  
Nadja Keller ◽  
Noriki Fujimoto ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Lymph Nodes ◽  
Single Cell ◽  
In Silico Analysis ◽  
Skin Inflammation ◽  
Lymphatic Endothelial Cells ◽  
Depth Analysis ◽  
Subcapsular Sinus ◽  
Transcriptional Changes ◽  
Sinus Floor

The lymphatic system plays a crucial role in immunity and lymph nodes (LNs) undergo drastic remodeling during inflammation. Here, we used single-cell RNA sequencing to investigate transcriptional changes in lymphatic endothelial cells (LECs) in LNs draining naïve and inflamed skin. We found that subsets of LECs lining the different LN sinuses responded individually to skin inflammation, suggesting that they exert distinct functions under pathological conditions. Among the genes dysregulated during inflammation, we confirmed an up-regulation of CD200 in the LECs lining the subcapsular sinus floor with a possible function in immune regulation. Furthermore, by in silico analysis, we predicted numerous possible interactions of LECs with diverse immune cells in the LNs and found similarities in the transcriptional changes of LN LECs in different skin inflammation settings. In summary, we provide an in-depth analysis of the transcriptional landscape of LN LECs in the naïve state and in skin inflammation.

scholarly journals Single-cell mapping reveals new markers and functions of lymphatic endothelial cells in lymph nodes

2020 ◽  
Author(s):  
Noriki Fujimoto ◽  
Yuliang He ◽  
Marco D’Addio ◽  
Carlotta Tacconi ◽  
Michael Detmar ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Immune Responses ◽  
Lymph Nodes ◽  
Single Cell ◽  
Cancer Metastasis ◽  
Lymphatic Vessels ◽  
Peripheral Tolerance ◽  
Lymphatic Endothelial Cells ◽  
Subcapsular Sinus ◽  
Lymphocyte Egress

ABSTRACTLymph nodes (LNs) are highly organized secondary lymphoid organs that mediate adaptive immune responses to antigens delivered via afferent lymphatic vessels. Lymphatic endothelial cells (LECs) line intranodal lymphatic sinuses and organize lymph and antigen distribution. LECs also directly regulate T cells, mediating peripheral tolerance to self-antigens, and play a major role in many diseases including cancer metastasis. However, little is known about the phenotypic and functional heterogeneity of LN LECs. Using single-cell RNA sequencing, we comprehensively defined the transcriptome of LECs in murine skin-draining LNs, and identified new markers and functions of distinct LEC subpopulations. We found that LECs residing in the subcapsular sinus have an unanticipated function in scavenging of modified LDL and also identified a specific cortical LEC subtype implicated in rapid lymphocyte egress from LNs. Our data provide new insights into the diversity of LECs in murine lymph nodes and a rich resource for future studies into the regulation of immune responses by lymph node LECs.

scholarly journals Single-cell mapping reveals new markers and functions of lymphatic endothelial cells in lymph nodes

PLoS Biology ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. e3000704 ◽  
Author(s):  
Noriki Fujimoto ◽  
Yuliang He ◽  
Marco D’Addio ◽  
Carlotta Tacconi ◽  
Michael Detmar ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Lymph Nodes ◽  
Single Cell ◽  
Lymphatic Endothelial Cells ◽  
Cell Mapping

scholarly journals Mapping the Distinctive Populations of Lymphatic Endothelial Cells in Different Zones of Human Lymph Nodes

PLoS ONE ◽  
2014 ◽  
Vol 9 (4) ◽  
pp. e94781 ◽  
Author(s):  
Saem Mul Park ◽  
Catherine E. Angel ◽  
Julie D. McIntosh ◽  
Claudia M. Mansell ◽  
Chun-Jen J. Chen ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Lymph Nodes ◽  
Lymphatic Endothelial Cells

scholarly journals Dense poly(ethylene glycol) coatings maximize nanoparticle transport across lymphatic endothelial cells

2020 ◽  
Author(s):  
Jacob McCright ◽  
Colin Skeen ◽  
Jenny Yarmovsky ◽  
Katharina Maisel
Keyword(s):  
Endothelial Cells ◽  
Ethylene Glycol ◽  
Lymph Nodes ◽  
Lymphatic Vessels ◽  
Lymphatic Endothelial Cells ◽  
Poly Ethylene Glycol ◽  
Nanoparticle Transport ◽  
Peripheral Tissues ◽  
Transport Efficiency ◽  
Poly Ethylene

AbstractLymphatic vessels have received considerable attention in recent years as delivery route for immune modulatory therapies to the lymph nodes. Lymph node targeting of immunotherapies and vaccines has been shown to significantly enhance their therapeutic efficacy. Lymphatics transport functions materials from peripheral tissues to the lymph nodes, including small 10 – 250 nm therapeutic nanoparticles. While size required to enter lymphatic vessels, surface chemistry is more poorly studied. Here, we probed the effects of surface poly(ethylene glycol) (PEG) density on nanoparticle transport across lymphatic endothelial cells (LECs). We differentially PEGylated model carboxylate-modified polystyrene nanoparticles to form either a brush or dense brush PEG conformation on the nanoparticle surfaces. Using an established in-vitro lymphatic transport model, we found that the addition of any PEG improved the transport of nanoparticles through lymphatic endothelial cells (2.5 - 2.6 ± 0.9% transport efficiency at 24 hours) compared to the unmodified PS-COOH nanoparticles (0.05 ± 0.05% transport efficiency at 24 hours). Additionally, we found that transcellular transport is maximized (4.2 ± 0.7% transport efficiency at 24 hours) when the PEG is in a dense brush conformation on nanoparticle surfaces, corresponding with a high grafting density (Rf/D = 4.9). These results suggest that PEG conformation has a crucial role in determining translocation of nanoparticles across LECs and into lymphatic vessels. Thus, we identified PEG density as a major design criteria for maximizing lymphatic targeting of therapeutic nanoparticle formulations that can be widely applied to enhance immunotherapeutic and vaccine outcomes in future studies.

scholarly journals Chemokine CCL2 facilitates ICAM-1-mediated interactions of cancer cells and lymphatic endothelial cells in sentinel lymph nodes

2009 ◽  
Vol 100 (3) ◽  
pp. 419-428 ◽  
Author(s):  
Yoshiko Kawai ◽  
Maki Kaidoh ◽  
Yumiko Yokoyama ◽  
Kenji Sano ◽  
Toshio Ohhashi
Keyword(s):  
Endothelial Cells ◽  
Lymph Nodes ◽  
Cancer Cells ◽  
Sentinel Lymph Nodes ◽  
Lymphatic Endothelial Cells

Tissue inflammation modulates gene expression of lymphatic endothelial cells and dendritic cell migration in a stimulus-dependent manner

Blood ◽  
2011 ◽  
Vol 118 (1) ◽  
pp. 205-215 ◽  
Author(s):  
Benjamin Vigl ◽  
David Aebischer ◽  
Maximilian Nitschké ◽  
Maria Iolyeva ◽  
Tamara Röthlin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Dendritic Cell ◽  
Lymph Nodes ◽  
Adhesion Molecules ◽  
Contact Hypersensitivity ◽  
Dependent Manner ◽  
Lymphatic Endothelial Cells ◽  
Tissue Inflammation ◽  
Draining Lymph Nodes

Abstract Chemokines and adhesion molecules up-regulated in lymphatic endothelial cells (LECs) during tissue inflammation are thought to enhance dendritic cell (DC) migration to draining lymph nodes, but the in vivo control of this process is not well understood. We performed a transcriptional profiling analysis of LECs isolated from murine skin and found that inflammation induced by a contact hypersensitivity (CHS) response up-regulated the adhesion molecules ICAM-1 and VCAM-1 and inflammatory chemokines. Importantly, the lymphatic markers Prox-1, VEGFR3, and LYVE-1 were significantly down-regulated during CHS. By contrast, skin inflammation induced by complete Freund adjuvant induced a different pattern of chemokine and lymphatic marker gene expression and almost no ICAM-1 up-regulation in LECs. Fluorescein isothiocyanate painting experiments revealed that DC migration to draining lymph nodes was more strongly increased in complete Freund adjuvant-induced than in CHS-induced inflammation. Surprisingly, DC migration did not correlate with the induction of CCL21 and ICAM-1 protein in LECs. Although the requirement for CCR7 signaling became further pronounced during inflammation, CCR7-independent signals had an additional, albeit moderate, impact on enhancing DC migration. Collectively, these findings indicate that DC migration in response to inflammation is stimulus-specific, mainly CCR7-dependent, and overall only moderately enhanced by LEC-induced genes other than CCL21.

scholarly journals D6 facilitates cellular migration and fluid flow to lymph nodes by suppressing lymphatic congestion

Blood ◽  
2011 ◽  
Vol 118 (23) ◽  
pp. 6220-6229 ◽  
Author(s):  
Kit Ming Lee ◽  
Clive S. McKimmie ◽  
Derek S. Gilchrist ◽  
Kenneth J. Pallas ◽  
Robert J. Nibbs ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Immune Responses ◽  
Lymph Nodes ◽  
Cellular Migration ◽  
Lymphatic Endothelial Cells ◽  
Adaptive Immune ◽  
Cc Chemokines ◽  
Antigen Presenting ◽  
Deficient Mice ◽  
Inflammatory Leukocytes

Abstract Lymphatic endothelial cells are important for efficient flow of antigen-bearing fluid and antigen-presenting cells (APCs) from peripheral sites to lymph nodes (LNs). APC movement to LNs is dependent on the constitutive chemokine receptor CCR7, although how conflicting inflammatory and constitutive chemokine cues are integrated at lymphatic surfaces during this process is not understood. Here we reveal a previously unrecognized aspect of the regulation of this process. The D6 chemokine-scavenging receptor, which is expressed on lymphatic endothelial cells (LECs), maintains lymphatic surfaces free of inflammatory CC-chemokines and minimizes interaction of inflammatory leukocytes with these surfaces. D6 does not alter the level of CCR7 ligands on LECs, thus ensuring selective presentation of homeostatic chemokines for interaction with CCR7+ APCs. Accordingly, in D6-deficient mice, inflammatory CC-chemokine adherence to LECs results in inappropriate perilymphatic accumulation of inflammatory leukocytes at peripheral inflamed sites and draining LNs. This results in lymphatic congestion and impaired movement of APCs, and fluid, from inflamed sites to LNs. We propose that D6, by suppressing inflammatory chemokine binding to lymphatic surfaces, and thereby preventing inappropriate inflammatory leukocyte adherence, is a key regulator of lymphatic function and a novel, and indispensable, contributor to the integration of innate and adaptive immune responses.

scholarly journals Lymphatic endothelial cells regulate B-cell homing to lymph nodes via a NIK-dependent mechanism

2018 ◽  
Vol 16 (2) ◽  
pp. 165-177 ◽  
Author(s):  
Jie Yang ◽  
Siya Zhang ◽  
Lingyun Zhang ◽  
Xiaoping Xie ◽  
Hui Wang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Lymph Nodes ◽  
B Cell ◽  
Lymphatic Endothelial Cells ◽  
Cell Homing ◽  
Dependent Mechanism
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