DC-SIGN (dendritic cell-specific ICAM-grabbing non-integrin) and DC-SIGN-related (DC-SIGNR): friend or foe?

2003 ◽  
Vol 104 (4) ◽  
pp. 437-446 ◽  
Author(s):  
Elizabeth J. SOILLEUX
Keyword(s):  
Endothelial Cells ◽  
Dendritic Cells ◽  
Dendritic Cell ◽  
T Lymphocytes ◽  
High Efficiency ◽  
Immunoglobulin E ◽  
Expression Patterns ◽  
Intercellular Adhesion Molecule ◽  
Carbohydrate Binding ◽  
Wide Range

C-type lectins are calcium-dependent carbohydrate-binding proteins with a wide range of biological functions, many of which are related to immunity. DC-SIGN (dendritic cell-specific ICAM-grabbing non-integrin, where ICAM is intercellular adhesion molecule) is a recently described mannose-specific C-type lectin expressed by dendritic cells. Dendritic cells are potent antigen-presenting cells capable of activating T-lymphocytes. DC-SIGN, which is expressed by dendritic cells, binds to ICAM-3 on T-lymphocytes, therefore playing an important role in the activation of T-lymphocytes. DC-SIGN can also bind HIV, and the virus may remain bound to DC-SIGN for protracted periods. DC-SIGN may deliver bound HIV to permissive cell types, mediating infection with high efficiency. A closely related C-type lectin, DC-SIGN-related molecule (DC-SIGNR) has also been described. DC-SIGNR is expressed by restricted subsets of endothelial cells, but has similar ICAM-3 and HIV-binding properties to DC-SIGN. This review describes the mapping of DC-SIGN and DC-SIGNR to chromosome 19p13.3 adjacent to the previously described C-type lectin, CD23 [the low-affinity receptor for immunoglobulin E (FcERII)]. The similar genomic organization of these three genes is discussed and consideration is given to the evolutionary duplications that may underlie this arrangement. Both DC-SIGN and DC-SIGNR possess a neck region, made up of multiple repeats, which supports the ligand-binding domain. Consideration is given to the biological reasons underlying the considerable polymorphism in the numbers of repeats in DC-SIGNR, but not DC-SIGN. The expression patterns of both DC-SIGN and DC-SIGNR are discussed in detail, with particular attention to the expression of both molecules in the placenta, which may have implications for the vertical transmission of HIV. Since dendritic cells may be important in determining the phenotype of many immune responses, via effects on T-lymphocytes, the differential expression of DC-SIGN by particular dendritic cell subsets may have important implications for the immunobiological functions of DC-SIGN. Similarly, the expression of DC-SIGNR by very restricted subsets of endothelial cells may give clues to the function of DC-SIGNR. Finally, the role of DC-SIGN in pathology, particularly in infective and neoplastic processes, is discussed, followed by speculation about likely future developments in this field.

Chrysin Suppresses Vascular Endothelial Inflammation via Inhibiting the NF-κB Signaling Pathway

2018 ◽  
Vol 24 (3) ◽  
pp. 278-287 ◽  
Author(s):  
Shengnan Zhao ◽  
Minglu Liang ◽  
Yilong Wang ◽  
Ji Hu ◽  
Yi Zhong ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Signaling Pathway ◽  
Adhesion Molecule ◽  
Intercellular Adhesion Molecule ◽  
Flavonoid Compound ◽  
Endothelial Inflammation ◽  
Wide Range

The vascular endothelium is a continuous layer of flat polygonal cells that are in direct contact with the blood and participate in responses to inflammation. Chrysin is a flavonoid compound extracted from plants of the genus Asteraceae with a wide range of pharmacological activities and physiological activities. Here, we studied the effects of chrysin on the regulation of the proadhesion and pro-inflammatory phenotypes of the endothelium both in vitro and in vivo. Our results revealed that chrysin strongly inhibited Tohoku Hospital Pediatrics-1 (THP-1) cell adhesion to primary human umbilical vein endothelial cells and concentration-dependently attenuated interleukin 1β-induced increases in intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin messenger RNA levels and ICAM-1 and VCAM-1 protein levels. Previous studies reported that nuclear factor κB (NF-κB) is important in the inflammatory response in endothelial cells, particularly in regulating adhesion molecules, and our data shed light on the mechanisms whereby chrysin suppressed endothelial inflammation via the NF-κB signaling pathway. In addition, our in vivo findings demonstrated the effects of chrysin in the permeability and inflammatory responses of the endothelium to inflammatory injury. Taken together, we conclude that chrysin inhibits endothelial inflammation both in vitro and in vivo, which could be mainly due to its inhibition of NF-κB signaling activation. In conclusion, chrysin may serve as a promising therapeutic candidate for inflammatory vascular diseases.

scholarly journals Kinetics and expression patterns of chemokine receptors in human CD4+ T lymphocytes primed by myeloid or plasmacytoid dendritic cells

2003 ◽  
Vol 33 (2) ◽  
pp. 474-482 ◽  
Author(s):  
Anja Langenkamp ◽  
Kinya Nagata ◽  
Kristine Murphy ◽  
Lijun Wu ◽  
Antonio Lanzavecchia ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Lymphocytes ◽  
Chemokine Receptors ◽  
Expression Patterns ◽  
Plasmacytoid Dendritic Cells

scholarly journals Dendritic Cell Production From Allogeneic Donor CD34+ Stem Cells and Mononuclear Cells for Patients With AML: Cancer Vaccine

2018 ◽  
Vol 4 (Supplement 2) ◽  
pp. 224s-224s
Author(s):  
A. Unal ◽  
A. Birekul ◽  
C. Unal ◽  
E. Karakus ◽  
Y. Köker
Keyword(s):  
Stem Cells ◽  
Dendritic Cells ◽  
Dendritic Cell ◽  
T Lymphocytes ◽  
Cancer Cells ◽  
Mononuclear Cells ◽  
Tumor Vaccine ◽  
Active Immunotherapy ◽  
Leukemic Stem Cells ◽  
Hla Dr

Background: Active immunotherapy provides better recognition of tumor-related antigens by immune system of patient, enhanced immune system and elimination of malignant cells. This modality employs therapeutic potential of donor specific and tumor specific immune responses. Active immunotherapy targets immunosuppressive and tolerogenic mechanisms suppressed by tumor cells. Aim: T lymphocytes and antigen-presenting cells (dendritic cells) are 2 cell lineages that play crucial role in the battle of organism against cancer. Close similarity between cancer cells and normal cell structure is the most important reason of escape from defense cells, namely T lymphocytes. Stimulation and enhancement of T lymphocytes against cancer cells comprise principal part of therapy. Methods: To generate allogeneic dendritic cells, leukemic stem cells were isolated from bone marrow samples from patients with acute leukemia. Lysate was prepared from leukemic stem cells identified by flow cytometer. Stem cells and mononuclear cells (1 × 10 > 6/kg) obtained from sibling donors by apheresis were separated to produce dendritic cells. For dendritic cell transformation, GM-CSF and IL-4 were added to media where leukemic stem cell lysate from patient and mononuclear cells from sibling donor were treated. From samples taken from the culture medium, after 48, 72 and 96 hours, dendritic cell surface markers (CD80, CD83 and CD86) was assessed by flow cytometry. CD3, CD14, CD19, CD56, CD66b-negative, and HLA-DR, CD86 positive are indicative of immature DC. HLA-DR, CD80 and CD83 positive are indicative of mature DC. Results: Mononuclear cells were detected by 27% among allogeneic hematopoietic cell groups harvested by apheresis. After culture under GMP conditions, mononuclear cell rate was found to be 24% on hours 96 and 120. It was seen that 88% of mononuclear cells transformed to mature dendritic cells after 96 hours culture. Conclusion: In cancer patients, minimal residual disease can be eliminated by active tumor vaccine after reducing tumor burden by standard methods. Tumor vaccine obtained from allogeneic sibling donor can be used in lieu of autologous tumor vaccine and it is thought to be more effective. Allogeneic dendritic cells produced at 37°C in CO2 media under GMP conditions can be used in tumor immunotherapy. More effective method would have been used by employing dendritic cells against cancer stem cells rather than cancer cells itself.

scholarly journals Dendritic Cell Production from Allogeneic Donor Cd34+ Stem Cells and Mononuclear Cells; Cancer Vaccine

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5723-5723 ◽  
Author(s):  
Ali Unal ◽  
Ayse Birekul ◽  
Mehmet Cagri Unal ◽  
Esen Karakus ◽  
Yavuz Köker ◽  
...  
Keyword(s):  
Stem Cells ◽  
Dendritic Cells ◽  
Dendritic Cell ◽  
T Lymphocytes ◽  
Cancer Cells ◽  
Mononuclear Cells ◽  
Tumor Vaccine ◽  
Active Immunotherapy ◽  
Leukemic Stem Cells ◽  
Hla Dr

Abstract Aim: Active immunotherapy provides better recognition of tumor-related antigens by immune system of patient, enhanced immune system and elimination of malignant cells. This modality employs therapeutic potential of donor specific and tumor specific immune responses. Active immunotherapy targets immunosuppressive and tolerogenic mechanisms suppressed by tumor cells. T lymphocytes and antigen-presenting cells (dendritic cells) are two cell lineages that play crucial role in the battle of organism against cancer. Close similarity between cancer cells and normal cell structure is the most important reason of escape from defense cells, namely T lymphocytes. Stimulation and enhancement of T lymphocytes against cancer cells comprise principal part of therapy. Material and Method: To generate allogeneic dendritic cells, leukemic stem cells were isolated from bone marrow samples from patients with acute leukemia. Lysate was prepared from leukemic stem cells identified by flow cytometer. Stem cells and mononuclear cells (1x10>6/kg) obtained from sibling donors by apheresis were separated to produce Dendritic Cells. For Dendritic Cell transformation, GM-CSF and IL-4 were added to media where leukemic stem cell lysate from patient and mononuclear cells from sibling donor were treated. From samples taken from the culture medium, after 48, 72 and 96 hours, dendritic cell surface markers (CD 80, CD 83 and CD 86) was assessed by flow cytometry. CD3, CD14, CD19, CD56, CD66b-negative, and HLA-DR, CD86 positive are indicative of immature DC. HLA-DR, CD 80 and CD83 positive are indicative of mature DC. Results: Mononuclear cells were detected by 27 % among allogeneic hematopoietic cell groups harvested by apheresis. After culture under GMP conditions, mononuclear cell rate was found to be 24% on hours 96 and 120. It was seen that 88% of mononuclear cells transformed to mature dendritic cells after 96 hours culture. Conclusion: In cancer patients, minimal residual disease can be eliminated by active tumor vaccine after reducing tumor burden by standard methods. Tumor vaccine obtained from allogeneic sibling donor can be used in lieu of autologous tumor vaccine and it is thought to be more effective. Allogeneic dendritic cells produced at 37¡C in CO2 media under GMP conditions can be used in tumor immunotherapy. More effective method would have been used by employing dendritic cells against cancer stem cells rather than cancer cells itself. Figure Mature dendritic cells (CD83+) Figure. Mature dendritic cells (CD83+) Disclosures No relevant conflicts of interest to declare.

scholarly journals Measles Virus Targets DC-SIGN To Enhance Dendritic Cell Infection

2006 ◽  
Vol 80 (7) ◽  
pp. 3477-3486 ◽  
Author(s):  
Lot de Witte ◽  
Marion Abt ◽  
Sibylle Schneider-Schaulies ◽  
Yvette van Kooyk ◽  
Teunis B. H. Geijtenbeek
Keyword(s):  
Dendritic Cells ◽  
Dendritic Cell ◽  
Respiratory Tract ◽  
Immune Suppression ◽  
Measles Virus ◽  
Viral Transmission ◽  
Intercellular Adhesion Molecule ◽  
Wild Type ◽  
Cell Infection ◽  
Specific Receptors

ABSTRACT Dendritic cells (DCs) are involved in the pathogenesis of measles virus (MV) infection by inducing immune suppression and possibly spreading the virus from the respiratory tract to lymphatic tissues. It is becoming evident that DC function can be modulated by the involvement of different receptors in pathogen interaction. Therefore, we have investigated the relative contributions of different MV-specific receptors on DCs to MV uptake into and infection of these cells. DCs express the MV receptors CD46 and CD150, and we demonstrate that the C-type lectin DC-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) is a novel receptor for laboratory-adapted and wild-type MV strains. The ligands for DC-SIGN are both MV glycoproteins F and H. In contrast to CD46 and CD150, DC-SIGN does not support MV entry, since DC-SIGN does not confer susceptibility when stably expressed in CHO cells. However, DC-SIGN is important for the infection of immature DCs with MV, since both attachment and infection of immature DCs with MV are blocked in the presence of DC-SIGN inhibitors. Our data demonstrate that DC-SIGN is crucial as an attachment receptor to enhance CD46/CD150-mediated infection of DCs in cis. Moreover, MV might not only target DC-SIGN to infect DCs but may also use DC-SIGN for viral transmission and immune suppression.

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