CD11c+ Dendritic Cells Rather than Langerhans Cells are Reduced in Normal Skin of Immunosuppressed Renal Transplant Recipients

Abstract

The increased risk of squamous cell carcinomas (SCC) in renal transplant recipients (RTR) is related to impaired immunosurveillance as a consequence of immunosuppressive therapy. Since dendritic cells (DC) play an important role in immunosurveillance, we investigated the quantity of DC subsets and macrophages in normal skin of RTR and immunocompetent controls by immunohistochemistry. In this comparative study Langerhans' cells (LC) were present in similar numbers in RTR and controls. The number of CD11c+ DC was significantly reduced in RTR, particularly in patients on triple treatment therapy, compared with controls. Macrophages were significantly increased. Plasmacytoid DC were not detected in normal skin. The reduced quantity of CD11c+ DC and increased number of macrophages in normal skin of immunosuppressed RTR may contribute to the increased incidence of SCC in RTR. This finding underlines the role of DC subsets in immunosurveillance, and may have implications for our understanding of the effect of immunosuppression on DC subsets.

Peritumoral dermis of squamous cell carcinomas in renal transplant recipients contains less CD11c+ myeloid dendritic cells and FoxP3+ T cells compared to immunocompetent controls

“…The number of peritumoral CD11c+ mDC was significantly reduced in RTR compared to immunocompetent controls. In a previous study, we also found a reduced number of CD11c+ mDC comparing normal skin of RTR to normal skin of immunocompetent controls . Therefore, immunosuppressive medication can most likely also influence DC.…”

“…We have previously analysed the number of CD11c+ mDC in normal skin of both RTR and immunocompetent individuals without SCC . Peritumoral dermis in both immunosuppressed RTR and immunocompetent controls was associated with high numbers of CD11c+ mDC.…”

“…In a previous study, we have shown that renal transplant recipients (RTR) have a significantly reduced number of CD11c+ mDC in normal looking skin compared to immunocompetent controls, which might contribute to the increased risk of SCC in RTR . The aim of this study was to quantify CD11c+ mDC, pDC, macrophages and FoxP3+ T cells in tissue immediately surrounding SCC, as well as LC in epithelial tumour nests from RTR compared to immunocompetent controls.…”

Langerhans Cells Facilitate UVB-Induced Epidermal Carcinogenesis

“…Recombinant IL-22 can promote the in vitro survival and proliferation of KCs after mechanical disruption ( Eyerich et al, 2009 ) and epidermal hypertrophy and dedifferentiation in reconstituted human epidermis ( Rabeony et al ., 2014 ). Since LC numbers are largely maintained in human AKs ( Shevchuk et al ., 2014 ) and epidermal LC levels in organ transplant recipients are equivalent to controls ( Sandvik et al , 2014 ), it is logical to investigate whether LC are contributing to human SCC development. Clearly, further studies are necessary to more fully elucidate the relationship of LC, ILC3, and IL-22 to epidermal homeostasis and UVB-induced cutaneous carcinogenesis.…”

Characterization of Monocyte‐Derived Dendritic Cells from Immunosuppressed Renal Transplant Recipients with and without Squamous Cell Carcinomas

“…One possible explanation for the increased risk of SCC might be impaired immune surveillance in RTR due to a reduction in DC subsets in blood [14][15][16][17] and in skin [18]. The immunosuppressive drugs affect not only T lymphocytes, but have also an effect on differentiation and maturation of DC, indicated by lower numbers and functional deficits of various circulating DC populations in immunosuppressed patients [17,[19][20][21][22].…”