An analysis of the function and expression of D6 on lymphatic endothelial cells.

doi:10.1182/blood-2012-04-425314

Paper

An analysis of the function and expression of D6 on lymphatic endothelial cells.

Published May 2, 2013 · C. McKimmie, Mark D. Singh, K. Hewit

Blood

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82

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6

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Abstract

The mechanisms by which CC chemokine receptor (CCR)7 ligands are selectively presented on lymphatic endothelium in the presence of inflammatory chemokines are poorly understood. The chemokine-scavenging receptor D6 is expressed on lymphatic endothelial cells (LEC) and contributes to selective presentation of CCR7 ligands by suppressing inflammatory chemokine binding to LEC surfaces. As well as preventing inappropriate inflammatory cell attachment to LECs, D6 is specifically involved in regulating the ability of LEC to discriminate between mature and immature dendritic cells (DCs). D6 overexpression reduces immature DC (iDC) adhesion to LECs, whereas D6 knockdown increases adhesion of iDCs that displace mature DCs. LEC D6 expression is regulated by growth factors, cytokines, and tumor microenvironments. In particular, interleukin-6 and interferon-γ are potent inducers, indicating a preferential role for D6 in inflamed contexts. Expression of the viral interleukin-6 homolog from Kaposi sarcoma-associated herpesvirus is also sufficient to induce significant D6 upregulation both in vitro and in vivo, and Kaposi sarcoma and primary effusion lymphoma cells demonstrate high levels of D6 expression. We therefore propose that D6, which is upregulated in both inflammatory and tumor contexts, is an essential regulator of inflammatory leukocyte interactions with LECs and is required for immature/mature DC discrimination by LECs.

In Vitro Study

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Study Snapshot

D6 is an essential regulator of inflammatory leukocyte interactions with lymphatic endothelial cells and plays a crucial role in immature/mature dendritic cell discrimination by LECs.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

An analysis of the function and expression of D6 on lymphatic endothelial cells.

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D6 plays a key role in lymphatic function by suppressing inflammatory chemokine binding and preventing inappropriate leukocyte adherence, facilitating efficient movement of antigen-presenting cells and fluid to lymph nodes.

Citations

The Role of vIL-6 in KSHV-Mediated Immune Evasion and Tumorigenesis

vIL-6 plays a crucial role in KSHV-mediated immune evasion and tumorigenesis, promoting the development of KSHV-associated diseases.

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ACKR2 prevents T cell expansion and tertiary lymphoid tissue formation, but is not essential to limit autoimmune tissue injury in lupus-prone B6lpr mice.

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Lymphatic endothelial cells play a crucial role in regulating immune responses in the tumor microenvironment, potentially enhancing anti-tumor immune responses through targeted therapies.

CXCL14 promotes metastasis of non-small cell lung cancer through ACKR2-depended signaling pathway

CXCL14 promotes lung cancer metastasis through a ACKR2-dependent signaling pathway, which can serve as a prognostic biomarker.

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ACKR2 plays a crucial role in regulating inflammation and neovascularization in herpes stromal keratitis, potentially offering a new treatment option for this blinding corneal disease.

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Conventional and atypical chemokine receptors differ in signaling properties, revealing potential targets for regulating ACKR2 and CCR5 function.

The Role of Atypical Chemokine Receptor D6 (ACKR2) in Physiological and Pathological Conditions; Friend, Foe, or Both?

ACKR2 plays a crucial role in maintaining fetal development, alleviating inflammation in various diseases, and potentially playing a tumor-promoting or tumor-suppressing role in cancer.

New Insights of CCR7 Signaling in Dendritic Cell Migration and Inflammatory Diseases

CCR7 signaling plays a crucial role in dendritic cell migration and inflammatory diseases, making it a potential target for immunotherapy and regulating dendritic cell migration.