Human embryonic epidermis contains a diverse Langerhans cell precursor pool

Abstract

Despite intense efforts, the exact phenotype of the epidermal Langerhans cell (LC) precursors during human ontogeny has not been determined yet. These elusive precursors are believed to migrate into the embryonic skin and to express primitive surface markers, including CD36, but not typical LC markers such as CD1a, CD1c and CD207. The aim of this study was to further characterize the phenotype of LC precursors in human embryonic epidermis and to compare it with that of LCs in healthy adult skin. We found that epidermal leukocytes in first trimester human skin are negative for CD34 and heterogeneous with regard to the expression of CD1c, CD14 and CD36, thus contrasting the phenotypic uniformity of epidermal LCs in adult skin. These data indicate that LC precursors colonize the developing epidermis in an undifferentiated state, where they acquire the definitive LC marker profile with time. Using a human three-dimensional full-thickness skin model to mimic in vivo LC development, we found that FACS-sorted, CD207-cord bloodderived haematopoietic precursor cells resembling foetal LC precursors but not CD14 + CD16-blood monocytes integrate into skin equivalents, and without additional exogenous cytokines give rise to cells that morphologically and phenotypically resemble LCs. Overall, it appears that CD14 -haematopoietic precursors possess a much higher differentiation potential than CD14 + precursor cells.

Human dendritic cell subsets: an update

“…The sequential formation of human fetal LC from myeloid precursors has been observed in detailed microscopic studies and ascribed to non-monocyte precursors. 166 In the steady state, the influence of TGF-b, E-cadherin/ b-catenin and the binding of Axl to gas 6 maintains LC in a quiescent state. 151,152,167,168 In postnatal life, local self-renewal restores LC numbers following chronic or low-grade inflammatory insults.…”

Pediatric dermatohistopathology – histopathology of skin diseases in newborns and infants

“…In the 8 th GW, melanocytes start migrating from the neuroectoderm, the neural crest, into the skin. Merkel cells and Langerhans cells are detectable in the epidermis from the 10 th -15 th GW onwards [19]. Subcutaneous adipose tissue starts forming in the 18 th GW (Figure 2d).…”

Langerhans cell histiocytosis is a neoplasm and consequently its recurrence is a relapse: In memory of Bob Arceci

“…Although equivalent studies cannot be carried out in humans, several reports suggest that human LCs share similar properties. In humans, the infiltration of embryonic dermis with LC precursors can be observed at early time points . Proliferating LCs were identified in human skin, and graft‐resident LCs were also found to remain for several years in a transplanted human limb graft .…”

“…In humans, the infiltration of embryonic dermis with LC precursors can be observed at early time points. 18 Proliferating LCs were identified in human skin, 19,20 and graft-resident LCs were also found to remain for several years in a transplanted human limb graft. 21 In addition, studies of hematopoietic stem cell recipients showed that LCs become donor-derived when there is inflammation due to graft versus host disease.…”