From bench to the bedside: how the study of cytokines in skin inflammation leads to keratinocyte transplantation in burns

The heart of the basic research activity of the LITEC is the study of the role of cytokines in skin inflammation induction mechanisms and interactions between inflammatory and keratinocytes. We highlighted the key role of a number of cytokines (IL-17 and IL-22, Oncostatin M (OSM), TNF and IL-1) on keratinocytes to induce an inflammatory phenotype including increased anti-bacterial activities, and cell differentiation inhibition. We demonstrated that the biological effects of each of these cytokine are unique, and that huge synergistic effects are observed when these cytokines are added together, even at low concentrations. We reported a strong cytokine dysregulation in psoriasis, that we were able to model in vitro. In this context, we need optimal source of keratinocytes to perform in vitro studies. We tested the regenerative keratinocyte capacities according to site donors, and we noted that keratinocytes from foreskin have the greatest proliferative and regenerative capacities, combined with expression of progenitor cell markers and low expression of epidermal differentiation markers. These results led us to use these preputial keratinocytes in suspension for graft in burned children. We purpose a successful method for grafting paediatric males presenting large severe burns through direct spreading of autologous foreskin keratinocytes. This alternative method is easy to implement, improves the quality of skin and minimizes associated donor site morbidity.