Effect of PI3K-gamma inhinition of human Langerhans cells

The potential involvement of PI3Kγ in immune-related diseases has been recently investigated leading to efforts in developing specific inhibitors of this isoform as therapeutic strategies. (Takeda et al 2010, Rommel et al 2007). Of particular significance to cutaneous disease, murine studies have indicated the importance of PI3Kγ in Langerhans cell (LC) function. Recently, it has been postulated, PI3Kγ is a molecular switch that controls immune suppression in macrophages, a cell type closely related to LCs. [Nature letter 2016]. In our analysis PIK3CG, encoding PI3Kγ was highly expressed by LC, in contrast to dermal dendritic cells (Polak et al 2014). Here we sought to examine the effect of PI3Kg inhibition on the function of human epidermal LCs. Human epidermal biopsies (n=2 biological donors) were treated with AS605240, a potent, cell-permeable and ATP-competitive inhibitor of PI3Kγ at the non-toxic dose 0.1uM for 48h.Migratory cells (>80% LCs) were processed for transcriptomic analysis