Human dendritic cells express neuronal Eph receptor tyrosine kinases: role of EphA2 in regulating adhesion to fibronectin

Saint‐Vis, Blandine de; Bouchet, C.; Gautier, Grégory; Valladeau, Jenny; Caux, Christophe; Garrone, Pierre

doi:10.1182/blood-2003-02-0500

Cited by 59 publications

(63 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Presence or absence of some markers were specific for skin DC subpopulations. 1) Epidermal LCs uniquely express very high levels of LGALS7 and langerin, as well as EFNB3, as previously shown by others (51). This is consistent with known expression of LGALS7 by epithelial cells (52).…”

Section: Discussionsupporting

confidence: 71%

Identification of Lineage Relationships and Novel Markers of Blood and Skin Human Dendritic Cells

Harman

Bye

Nasr

et al. 2013

The Journal of Immunology

View full text Add to dashboard Cite

The lineage relationships and fate of human dendritic cells (DCs) have significance for a number of diseases including HIV where both blood and tissue DCs may be infected. We used gene expression profiling of human monocyte and DC subpopulations sorted directly from blood and skin to define the lineage relationships. We also compared these with monocyte-derived DCs (MDDCs) and MUTZ3 Langerhans cells (LCs) to investigate their relevance as model skin DCs. Hierarchical clustering analysis showed that myeloid DCs clustered according to anatomical origin rather than putative lineage. Plasmacytoid DCs formed the most discrete cluster, but ex vivo myeloid cells formed separate clusters of cells both in blood and in skin. Separate and specific DC populations could be determined within skin, and the proportion of CD14+ dermal DCs (DDCs) was reduced and CD1a+ DDCs increased during culture, suggesting conversion to CD1a+-expressing cells in situ. This is consistent with origin of the CD1a+ DDCs from a local precursor rather than directly from circulating blood DCs or monocyte precursors. Consistent with their use as model skin DCs, the in vitro–derived MDDC and MUTZ3 LC populations grouped within the skin DC cluster. MDDCs clustered most closely to CD14+ DDCs; furthermore, common unique patterns of C-type lectin receptor expression were identified between these two cell types. MUTZ3 LCs, however, did not cluster closely with ex vivo–derived LCs. We identified differential expression of novel genes in monocyte and DC subsets including genes related to DC surface receptors (including C-type lectin receptors, TLRs, and galectins).

show abstract

Section: Discussionsupporting

confidence: 71%

Identification of Lineage Relationships and Novel Markers of Blood and Skin Human Dendritic Cells

Harman

Bye

Nasr

et al. 2013

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…To our knowledge, our results are the first to show that EPHA7 is a target of hypermethylation and silencing in mature B-cell lymphomas. Earlier reports indicate that EPHA7 is not expressed in peripheral B lymphocytes (Aasheim et al, 1997;de Saint-Vis et al, 2003). However, our findings are not inconsistent with these prior studies, for RT-PCR primers used in prior studies would not have amplified the variant EphA7-S transcript described here.…”

Section: Discussioncontrasting

confidence: 47%

Global DNA methylation profiling reveals silencing of a secreted form of Epha7 in mouse and human germinal center B-cell lymphomas

et al. 2007

View full text Add to dashboard Cite

Most human lymphomas originate from transformed germinal center (GC) B lymphocytes. While activating mutations and translocations of MYC, BCL2 and BCL6 promote specific GC lymphoma subtypes, other genetic and epigenetic modifications that contribute to malignant progression in the GC remain poorly defined. Recently, aberrant expression of the TCL1 proto-oncogene was identified in major GC lymphoma subtypes. TCL1 transgenic mice offer unique models of both aggressive GC and marginal zone B-cell lymphomas, further supporting a role for TCL1 in B-cell transformation. Here, restriction landmark genomic scanning was employed to discover tumor-associated epigenetic alterations in malignant GC and marginal zone B-cells in TCL1 transgenic mice. Multiple genes were identified that underwent DNA hypermethylation and decreased expression in TCL1 transgenic tumors. Further, we identified a secreted isoform of EPHA7, a member of the Eph family of receptor tyrosine kinases that are able to influence tumor invasiveness, metastasis and neovascularization. EPHA7 was hypermethylated and repressed in both mouse and human GC B-cell non-Hodgkin lymphomas, with the potential to influence tumor progression and spread. These data provide the first set of hypermethylated genes with the potential to complement TCL1-mediated GC B-cell transformation and spread.

show abstract

“…18 EphA2, EphA7 and EphB3 are expressed in Langerhans cells of the skin. 19 In the latter study, EphA2, ephrin-A3, ephrin-B1 and ephrin-B2 were also detected in keratinocytes.…”

Section: Discussionmentioning

confidence: 87%

Expression profile of Eph receptors and ephrin ligands in human skin and downregulation of EphA1 in nonmelanoma skin cancer

et al. 2006

View full text Add to dashboard Cite

Eph receptors and ephrin ligands represent the largest family of receptor tyrosine kinases. Beyond their welldefined meaning in developmental processes, these molecules also have important functions in adult human tissues and cancer. However, the Eph/ephrin expression profile in human skin is only marginally studied. We therefore investigated the mRNA expression of 21 Eph receptors and ephrin ligands in adult human skin in comparison to 13 other adult human tissues using quantitative real-time RT-PCR. In addition, immunohistochemistry was established for some members (EphA1, EphA2 and EphA7) to confirm the results of the RT-PCR and to identify the expressing cells in the skin. We found all investigated family members expressed in human skin, but at highly varying levels. EphA1, EphB3 and ephrin-A3 turned out to be most prominently expressed in skin compared to other adult human tissues. EphA1 was exclusively expressed in the epidermis. We therefore investigated the expression of EphA1 in nonmelanoma skin cancers derived from the epidermis (56 basal cell carcinomas and 32 squamous cell carcinomas). As demonstrated by immunohistochemistry, both skin cancers displayed a significant downregulation of EphA1 compared to the normal epidermis. In squamous cell carcinoma, the EphA1 downregulation was associated with increased tumor thickness, although this was not significant. Our results indicate that Eph receptors and ephrin ligands are widely expressed in the adult human skin, particularly in the epidermis, and may play an important role in skin homeostasis. EphA1 seems to be a marker of the differentiated normal epidermis and its downregulation in nonmelanoma skin cancer may contribute to carcinogenesis of these very frequent human tumors. EphA1 represents a new potential prognostic marker and therapeutic target in nonmelanoma skin cancer. Keywords: Eph receptor tyrosine kinase; ephrin; real-time RT-PCR; nonmelanoma skin cancer; EphA1; epidermis The Eph receptors represent the largest family of receptor tyrosine kinases. Eph receptors and their ephrin ligands are divided into the two subclasses A and B, based on the sequence homology of the extracellular sequence, the structure and the binding affinity.

show abstract

Human dendritic cells express neuronal Eph receptor tyrosine kinases: role of EphA2 in regulating adhesion to fibronectin

Cited by 59 publications

References 60 publications

Identification of Lineage Relationships and Novel Markers of Blood and Skin Human Dendritic Cells

Identification of Lineage Relationships and Novel Markers of Blood and Skin Human Dendritic Cells

Global DNA methylation profiling reveals silencing of a secreted form of Epha7 in mouse and human germinal center B-cell lymphomas

Expression profile of Eph receptors and ephrin ligands in human skin and downregulation of EphA1 in nonmelanoma skin cancer

Contact Info

Product

Resources

About