E-cadherin-dependent adhesion of dendritic and Langerhans cells to keratinocytes is defective in cervical human papillomavirus-associated (pre)neoplastic lesions.
Although human papillomavirus (HPV) DNA is detected in the majority of squamous intraepithelial lesions (SILs) and squamous cell carcinomas (SCCs) of the uterine cervix, the persistence and progression of cervical lesions suggest that viral antigens are not adequately presented to the immune system. This hypothesis is reinforced by the observation that most SILs show quantitative and functional alterations of Langerhans cells (LCs). The aim of this study was to determine whether modulation of E-cadherin-mediated homophilic and heterotypic interactions between keratinocytes and LCs is involved in these abnormalities of LCs in (pre)neoplastic cervical epithelium. Cell membrane expression of E-cadherin and the density of CD1a+ LCs were low in the epithelium of SILs and SCC biopsy specimens, compared with normal exocervical epithelium. Dendritic cells (DCs) and LCs generated in vitro were randomly distributed throughout the full thickness of organotypic cultures of E-cadherin- HPV-transformed cells. In contrast, these cells rapidly adhered to the keratinocyte cell layers when HPV-transformed cells transfected with E-cadherin were used. These data suggest that the E-cadherin-mediated contact between keratinocytes and LCs is potentially important for initiating or maintaining the immune response during chronic HPV infection.
Hubert
Pascale
P
Department of Pathology, CRCE, B35, CHU Sart Tilman, 4000 Liège, Belgium.
Caberg
Jean-Hubert
JH
Gilles
Christine
C
Bousarghin
Latifa
L
Franzen-Detrooz
Elizabeth
E
Boniver
Jacques
J
Delvenne
Philippe
P
D018949:Antigens, CD1 / Q000276:immunology; D015820:Cadherins / Q000032:analysis*; D002278:Carcinoma in Situ / Q000235:genetics / Q000503:physiopathology / Q000821:virology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000503:physiopathology / Q000821:virology; D002448:Cell Adhesion / Q000502:physiology; D002462:Cell Membrane / Q000473:pathology; D003713:Dendritic Cells / Q000473:pathology / Q000502:physiology*; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D015603:Keratinocytes / Q000473:pathology / Q000502:physiology*; D007801:Langerhans Cells / Q000473:pathology / Q000502:physiology*; D030361:Papillomavirus Infections / Q000235:genetics / Q000503:physiopathology*; D010641:Phenotype; D014162:Transfection; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000503:physiopathology* / Q000821:virology
D018949:Antigens, CD1; C419393:CD1a antigen; D015820:Cadherins