Human Lymphatic Endothelial Cells Express Multiple Functional TLRs

The lymphatic endothelium is the preferred route for the drainage of interstitial fluid from tissues and also serves as a conduit for peripheral dendritic cells (DCs) to reach draining lymph nodes. Lymphatic endothelial cells (LECs) are known to produce chemokines that recruit Ag-loaded DCs to lymph...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2008-03, Vol.180 (5), p.3399-3405
Main Authors: Pegu, Amarendra, Qin, Shulin, Fallert Junecko, Beth A, Nisato, Riccardo E, Pepper, Michael S, Reinhart, Todd A
Format: Article
Language:English
Subjects:
Animals
Cell Adhesion Molecules - biosynthesis
Cell Line
Cells, Cultured
Chemokine CCL21 - biosynthesis
Chemokine CCL21 - genetics
Chemokines - biosynthesis
Chemokines - physiology
Cytokines - biosynthesis
Cytokines - physiology
Dose-Response Relationship, Immunologic
Endothelium, Lymphatic - cytology
Endothelium, Lymphatic - immunology
Endothelium, Lymphatic - metabolism
Humans
Inflammation Mediators - metabolism
Inflammation Mediators - physiology
Ligands
Lung - cytology
Lung - immunology
Lung - metabolism
Mice
Microcirculation - cytology
Microcirculation - immunology
Microcirculation - metabolism
Skin - cytology
Skin - immunology
Skin - metabolism
Toll-Like Receptors - biosynthesis
Toll-Like Receptors - metabolism
Toll-Like Receptors - physiology
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Summary:The lymphatic endothelium is the preferred route for the drainage of interstitial fluid from tissues and also serves as a conduit for peripheral dendritic cells (DCs) to reach draining lymph nodes. Lymphatic endothelial cells (LECs) are known to produce chemokines that recruit Ag-loaded DCs to lymphatic vessels and therefore are likely to regulate the migration of DCs to lymph nodes. TLRs are immune receptors that recognize pathogen associated molecular patterns and then signal and stimulate production of inflammatory chemokines and cytokines that contribute to innate and adaptive immune responses. TLRs are known to be expressed by a wide variety of cell types including leukocytes, epithelial cells, and endothelial cells. Because the TLR expression profile of LECs remains largely unexamined, we have undertaken a comprehensive study of the expression of TLR1-10 mRNAs and protein in primary human dermal (HD) and lung LECs as well as in htert-HDLECs, which display a longer life-span than HDLECs. We found that all three cell types expressed TLR1-6 and TLR9. The responsiveness of these LECs to a panel of ligands for TLR1-9 was measured by real-time RT-PCR, ELISA, and flow cytometry, and revealed that the LECs responded to most but not all TLR ligands by increasing expression of inflammatory chemokines, cytokines, and adhesion molecules. These findings provide insight into the ability of cells of the lymphatic vasculature to respond to pathogens and potential vaccine adjuvants and shape peripheral environments in which DCs will acquire Ag and environmental cues.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.180.5.3399