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

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.

IL-15 regulates immature B-cell homing in an Ly49D-, IL-12–, and IL-18–dependent manner

Blood ◽  
2008 ◽  
Vol 111 (1) ◽  
pp. 50-59 ◽  
Author(s):  
Gili Hart ◽  
Tamar Avin-Wittenberg ◽  
Idit Shachar
Keyword(s):  
Immune Response ◽  
B Cells ◽  
Lymph Nodes ◽  
B Cell ◽  
Dependent Manner ◽  
Cell Repertoire ◽  
Cell Homing ◽  
Final Maturation ◽  
Immature B Cells ◽  
Ifn Γ

To complete their maturation and participate in the humoral immune response, immature B cells that leave the bone marrow are targeted to specific areas in the spleen, where they differentiate into mature cells. Previously, we showed that immature B cells actively down-regulate their integrin-mediated migration to lymph nodes or to sites of inflammation, enabling their targeting to the spleen for final maturation. This inhibition is mediated by IFN-γ, which is transcribed and secreted at low levels by these immature B cells; IFN-γ expression is extinguished following B-cell maturation. Stimulation of the MHC class I receptor, Ly49D, triggers a signaling cascade that increases transcription of both IL-12 (p40) and IL-18; these, in turn, induce the secretion of IFN-γ. In the present study, we demonstrate that Ly49D-dependent secretion of IL-12 and IL-18 induces IL-15 expression by immature B cells, and that these 3 factors together regulate IFN-γ production that inhibits their ability to home to the lymph nodes or to sites of inflammation. Thus, IL-15 controls immature B-cell homing, resulting in shaping the B-cell repertoire to enable an efficient immune response.

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 Chemokine Requirements for B Cell Entry to Lymph Nodes and Peyer's Patches

2002 ◽  
Vol 196 (1) ◽  
pp. 65-75 ◽  
Author(s):  
Takaharu Okada ◽  
Vu N. Ngo ◽  
Eric H. Ekland ◽  
Reinhold Förster ◽  
Martin Lipp ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
B Cell ◽  
Chemokine Receptor ◽  
Cell Entry ◽  
Peyer's Patches ◽  
Peyer’S Patches ◽  
Wild Type ◽  
High Endothelial Venules ◽  
Cell Homing ◽  
T Cell Homing

B cell entry to lymph nodes and Peyer's patches depends on chemokine receptor signaling, but the principal chemokine involved has not been defined. Here we show that the homing of CXCR4−/− B cells is suppressed in CCL19 (ELC)- and CCL21 (SLC)-deficient paucity of lymph node T cells mice, but not in wild-type mice. We also find that CXCR4 can contribute to T cell homing. Using intravital microscopy, we find that B cell adhesion to high endothelial venules (HEVs) is disrupted when CCR7 and CXCR4 are predesensitized. In Peyer's patches, B cell entry is dependent on CXCR5 in addition to CCR7/CXCR4. CXCL12 (SDF1) is displayed broadly on HEVs, whereas CXCL13 (BLC) is found selectively on Peyer's patch follicular HEVs. These findings establish the principal chemokine and chemokine receptor requirements for B cell entry to lymph nodes and Peyer's patches.

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.

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