Cross Talk between Lymph Node Lymphatic Endothelial Cells and T Cells in Inflammation and Cancer

2017 ◽  
Keyword(s):  
T Cells ◽  
Endothelial Cells ◽  
Lymph Node ◽  
Cross Talk ◽  
Lymphatic Endothelial Cells

scholarly journals Lymph node–resident lymphatic endothelial cells mediate peripheral tolerance via Aire-independent direct antigen presentation

2010 ◽  
Vol 207 (4) ◽  
pp. 681-688 ◽  
Author(s):  
Jarish N. Cohen ◽  
Cynthia J. Guidi ◽  
Eric F. Tewalt ◽  
Hui Qiao ◽  
Sherin J. Rouhani ◽  
...  
Keyword(s):  
T Cells ◽  
Endothelial Cells ◽  
Lymph Node ◽  
Immune Tolerance ◽  
Negative Selection ◽  
Specific Protein ◽  
Peripheral Tolerance ◽  
Lymphatic Endothelial Cells ◽  
Cross Presentation ◽  
Tissue Antigens

Peripheral immune tolerance is generally thought to result from cross-presentation of tissue-derived proteins by quiescent tissue-resident dendritic cells to self-reactive T cells that have escaped thymic negative selection, leading to anergy or deletion. Recently, we and others have implicated the lymph node (LN) stroma in mediating CD8 T cell peripheral tolerance. We demonstrate that LN-resident lymphatic endothelial cells express multiple peripheral tissue antigens (PTAs) independent of the autoimmune regulator (Aire). They directly present an epitope derived from one of these, the melanocyte-specific protein tyrosinase, to tyrosinase-specific CD8 T cells, leading to their deletion. We also show that other LN stromal subpopulations express distinct PTAs by mechanisms that vary in their Aire dependence. These results establish lymphatic endothelial cells, and potentially other LN-resident cells, as systemic mediators of peripheral immune tolerance.

scholarly journals HIV-1 Matrix Protein p17 Promotes Lymphangiogenesis and Activates the Endothelin-1/Endothelin B Receptor Axis

2014 ◽  
Vol 34 (4) ◽  
pp. 846-856 ◽  
Author(s):  
Francesca Caccuri ◽  
Christine Rueckert ◽  
Cinzia Giagulli ◽  
Kai Schulze ◽  
Daniele Basta ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Lymph Node ◽  
Structure Formation ◽  
Highly Active Antiretroviral Therapy ◽  
Matrix Protein ◽  
Lymphatic Endothelial Cells ◽  
Endothelin 1 ◽  
Tumor Dissemination ◽  
Hiv 1

Objective— AIDS-related lymphomas are high grade and aggressively metastatic with poor prognosis. Lymphangiogenesis is essential in supporting proliferation and survival of lymphoma, as well as tumor dissemination. Data suggest that aberrant lymphangiogenesis relies on action of HIV-1 proteins rather than on a direct effect of the virus itself. HIV-1 matrix protein p17 was found to accumulate and persist in lymph nodes of patients even under highly active antiretroviral therapy. Because p17 was recently found to exert a potent proangiogenic activity by interacting with chemokine (C-X-C motif) receptors 1 and 2, we tested the prolymphangiogenic activity of the viral protein. Approach and Results— Human primary lymph node–derived lymphatic endothelial cells were used to perform capillary-like structure formation, wound healing, spheroids, and Western blot assays after stimulation with or without p17. Here, we show that p17 promotes lymphangiogenesis by binding to chemokine (C-X-C motif) receptor-1 and chemokine (C-X-C motif) receptor-2 expressed on lymph node–derived lymphatic endothelial cells and activating the Akt/extracellular signal–regulated kinase signaling pathway. In particular, it was found to induce capillary-like structure formation, sprout formation from spheroids, and increase lymph node–derived lymphatic endothelial cells motility. The p17 lymphangiogenic activity was, in part, sustained by activation of the endothelin-1/endothelin receptor B axis. A Matrigel plug assay showed that p17 was able to promote the outgrowth of lymphatic vessels in vivo, demonstrating that p17 directly regulates lymphatic vessel formation. Conclusions— Our results suggest that p17 may generate a prolymphangiogenic microenvironment and plays a role in predisposing the lymph node to lymphoma growth and metastasis. This finding offers new opportunities to identify treatment strategies in combating AIDS-related lymphomas.

scholarly journals Lymphatic Endothelial Cells Control Initiation of Lymph Node Organogenesis

Immunity ◽  
2017 ◽  
Vol 47 (1) ◽  
pp. 80-92.e4 ◽  
Author(s):  
Lucas Onder ◽  
Urs Mörbe ◽  
Natalia Pikor ◽  
Mario Novkovic ◽  
Hung-Wei Cheng ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Lymph Node ◽  
Lymphatic Endothelial Cells

scholarly journals Tolerogenic Properties of Lymphatic Endothelial Cells Are Controlled by the Lymph Node Microenvironment

PLoS ONE ◽  
2014 ◽  
Vol 9 (2) ◽  
pp. e87740 ◽  
Author(s):  
Jarish N. Cohen ◽  
Eric F. Tewalt ◽  
Sherin J. Rouhani ◽  
Erica L. Buonomo ◽  
Amber N. Bruce ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Lymph Node ◽  
Lymphatic Endothelial Cells

scholarly journals Brain-to-cervical lymph node signaling after stroke

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Elga Esposito ◽  
Bum Ju Ahn ◽  
Jingfei Shi ◽  
Yoshihiko Nakamura ◽  
Ji Hyun Park ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Lymph Node ◽  
Cerebral Ischemia ◽  
Systemic Inflammation ◽  
Cervical Lymph Node ◽  
Inflammatory Responses ◽  
Focal Cerebral Ischemia ◽  
Brain Infarction ◽  
Surgical Removal ◽  
Lymphatic Endothelial Cells

AbstractAfter stroke, peripheral immune cells are activated and these systemic responses may amplify brain damage, but how the injured brain sends out signals to trigger systemic inflammation remains unclear. Here we show that a brain-to-cervical lymph node (CLN) pathway is involved. In rats subjected to focal cerebral ischemia, lymphatic endothelial cells proliferate and macrophages are rapidly activated in CLNs within 24 h, in part via VEGF-C/VEGFR3 signalling. Microarray analyses of isolated lymphatic endothelium from CLNs of ischemic mice confirm the activation of transmembrane tyrosine kinase pathways. Blockade of VEGFR3 reduces lymphatic endothelial activation, decreases pro-inflammatory macrophages, and reduces brain infarction. In vitro, VEGF-C/VEGFR3 signalling in lymphatic endothelial cells enhances inflammatory responses in co-cultured macrophages. Lastly, surgical removal of CLNs in mice significantly reduces infarction after focal cerebral ischemia. These findings suggest that modulating the brain-to-CLN pathway may offer therapeutic opportunities to ameliorate systemic inflammation and brain injury after stroke.

Lymph node‐derived lymphatic endothelial cells express functional costimulatory molecules and impair dendritic cell‐induced allogenic T‐cell proliferation

2012 ◽  
Vol 26 (7) ◽  
pp. 2835-2846 ◽  
Author(s):  
Miriam Nörder ◽  
Maximiliano G. Gutierrez ◽  
Sonia Zicari ◽  
Edoardo Cervi ◽  
Arnaldo Caruso ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cells ◽  
Lymph Node ◽  
T Cell ◽  
Dendritic Cell ◽  
Costimulatory Molecules ◽  
T Cell Proliferation ◽  
Lymphatic Endothelial Cells

scholarly journals Targeting Receptor Tyrosine Kinase on Lymphatic Endothelial Cells for the Therapy of Colon Cancer Lymph Node Metastasis

Neoplasia ◽  
2006 ◽  
Vol 8 (9) ◽  
pp. 747-757 ◽  
Author(s):  
Robert B. Rebhun ◽  
Robert R. Langley ◽  
Kenji Yokoi ◽  
Dominic Fan ◽  
Jeffrey E. Gershenwald ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Endothelial Cells ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Lymphatic Endothelial Cells ◽  
Node Metastasis

scholarly journals In Sickness and in Health: The Immunological Roles of the Lymphatic System

2021 ◽  
Vol 22 (9) ◽  
pp. 4458
Author(s):  
Louise A. Johnson
Keyword(s):  
Endothelial Cells ◽  
Lymph Node ◽  
Lymphatic System ◽  
Immune Cell ◽  
Immune Surveillance ◽  
Intercellular Junctions ◽  
Peripheral Tissue ◽  
Lymphatic Endothelial Cells ◽  
High Endothelial Venules ◽  
Immune Cell Subsets

The lymphatic system plays crucial roles in immunity far beyond those of simply providing conduits for leukocytes and antigens in lymph fluid. Endothelial cells within this vasculature are distinct and highly specialized to perform roles based upon their location. Afferent lymphatic capillaries have unique intercellular junctions for efficient uptake of fluid and macromolecules, while expressing chemotactic and adhesion molecules that permit selective trafficking of specific immune cell subsets. Moreover, in response to events within peripheral tissue such as inflammation or infection, soluble factors from lymphatic endothelial cells exert “remote control” to modulate leukocyte migration across high endothelial venules from the blood to lymph nodes draining the tissue. These immune hubs are highly organized and perfectly arrayed to survey antigens from peripheral tissue while optimizing encounters between antigen-presenting cells and cognate lymphocytes. Furthermore, subsets of lymphatic endothelial cells exhibit differences in gene expression relating to specific functions and locality within the lymph node, facilitating both innate and acquired immune responses through antigen presentation, lymph node remodeling and regulation of leukocyte entry and exit. This review details the immune cell subsets in afferent and efferent lymph, and explores the mechanisms by which endothelial cells of the lymphatic system regulate such trafficking, for immune surveillance and tolerance during steady-state conditions, and in response to infection, acute and chronic inflammation, and subsequent resolution.

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