Lipid raft-enriched stem cell-like keratinocytes in the epidermis, hair follicles and sinus tracts in hidradenitis suppurativa.
Hidradenitis suppurativa (HS) is a disease, that causes considerable morbidity in patients. A histological hallmark of the disorder is the formation of sinus tracts in the dermis and the subcutis. Biologically, they represent a poorly understood phenomenon involving the infiltrative growth of proliferating non-malignant keratinocytes. Lipid domains in plasma membranes (lipid rafts) play a role in the function of growth factors and are suspected of having a pathogenic role in cell migration and invasive growth. Using HS as a model, the presence of lipid rafts was studied using cholera toxin conjugated with FITC (CTx-FITC) and antibeta1 integrin (CD29)-CyChrome conjugate fluorescence staining of unfixed and acetone-fixed cryostat sections of lesional and paralesional skin samples. The double-labeled skin samples were observed in the confocal laser-scanning fluorescence microscope. Samples were obtained from five patients with HS. The lesional epidermis of HS contained three populations of keratinocytes: CD29(bright)CTx(dim), CD29(dim)CTx(bright) and a third hitherto unseen population containing double-positive CD29(bright)CTx(bright) cells. The CD29(bright)CTx(dim) population resembles the earlier described epidermal stem-like cells, while the CD29(dim)CTx(bright) basal keratinocytes overlap with the transit-amplifying cell pool. The new population of double-positive CD29(bright)CTx(bright) cells was localized on the slopes of the papillas, focally in the suprabasal epidermal layers, in some hair follicles and in the majority of sinus tracts. Such double-positive cells have not previously been encountered by us in normal epidermis and hair follicles. Using HS as a model, it is suggested that the keratinocytes involved in sinus tract formation are CD29(bright)CTx(bright) cells. Owing to the physical proximity of the cells, it is hypothesised that the described CD29(bright)CTx(bright) cells result from an increased expression of CD29 on the CTx(bright) cells. It is likely that the double-positive CD29(bright)CTx(bright) cells emerge due to the influence of local inflammatory cytokines. Sinus tract formation may represent an aberrant epidermal repair response executed by the activated CD29(bright)CTx(bright) keratinocytes capable of non-malignant infiltrative growth in the dermis and subcutis.
Gniadecki
Robert
R
Department of Dermatology, Bispebjerg Hospital, Copenhagen,Denmark.
Jemec
Gregor B E
GB
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005456:Fluorescent Dyes; D018859:Hair Follicle / Q000473:pathology*; D017497:Hidradenitis Suppurativa / Q000473:pathology*; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology*; D021962:Membrane Microdomains / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D013234:Stem Cells / Q000473:pathology*
D005456:Fluorescent Dyes; D019012:Integrin beta1