Human dendritic cells express neuronal Eph receptor tyrosine kinases: role of EphA2 in regulating adhesion to fibronectin.
Eph receptor tyrosine kinases and their ligands, the ephrins, have been primarily described in the nervous system for their roles in axon guidance, development, and cell intermingling. Here we address whether Eph receptors may also regulate dendritic cell (DC) trafficking. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that DCs derived from CD34+ progenitors, but not from monocytes, expressed several receptors, in particular EphA2, EphA4, EphA7, EphB1, and EphB3 mRNA. EphB3 was specifically expressed by Langerhans cells, and EphA2 and EphA7 were expressed by both Langerhans- and interstitial-type DCs. EphA and EphB protein expression on DCs generated in vitro was confirmed by staining with ephrin-A3-Fc and ephrin-B3-Fc fusion proteins that bind to different Eph members, in particular EphA2 and EphB3. Immunostaining with anti-EphA2 antibodies demonstrated the expression of EphA2 by immature DCs and by skin Langerhans cells isolated ex vivo. Interestingly, ephrin expression was detected in epidermal keratinocytes and also in DCs. Adhesion of CD34+-derived DCs to fibronectin, but not to poly-l-lysine, was increased in the presence of ephrin-A3-Fc, a ligand of EphA2, through a beta1 integrin activation pathway. As such, EphA2/ephrin-A3 interactions may play a role in the localization and network of Langerhans cells in the epithelium and in the regulation of their trafficking.
de Saint-Vis
Blandine
B
Laboratory for Immunological Research, Schering-Plough, 27 chemin des peupliers, BP 11, 69571 Dardilly, France. blandine.de.saint.vis@spcorp.com
Bouchet
Caroline
C
Gautier
Gregory
G
Valladeau
Jenny
J
Caux
Christophe
C
Garrone
Pierre
P
D018952:Antigens, CD34 / Q000032:analysis; D002448:Cell Adhesion / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage; D002465:Cell Movement; D003713:Dendritic Cells / Q000166:cytology / Q000201:enzymology*; D036383:Ephrin-A2 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D036385:Ephrin-A4 / Q000096:biosynthesis / Q000235:genetics; D036387:Ephrin-B1 / Q000096:biosynthesis / Q000235:genetics; D036389:Ephrin-B3 / Q000096:biosynthesis / Q000235:genetics; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology; D005353:Fibronectins / Q000737:chemistry*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D019012:Integrin beta1 / Q000502:physiology; D015603:Keratinocytes / Q000201:enzymology; D007801:Langerhans Cells / Q000166:cytology / Q000201:enzymology; D011107:Polylysine / Q000737:chemistry; D036081:Receptors, Eph Family / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D018952:Antigens, CD34; D036383:Ephrin-A2; D036385:Ephrin-A4; D036387:Ephrin-B1; D036389:Ephrin-B3; D005353:Fibronectins; D019012:Integrin beta1; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D011107:Polylysine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D036081:Receptors, Eph Family