Transforming growth factor-β1 regulates the expression of the high-affinity receptor for IgE on CD34+ stem cell-derived CD1a + dendritic cells in vitro

Abstract

It has been reported that monocytes, Langerhans cells (LC) and other dendritic cells (DC) express the high-affinity receptor for IgE (FcεRI) in patients with atopic diseases. These cells may be instrumental in the control of the immune response and the allergic inflammation. In this context, transforming growth factor beta 1 (TGF-β1) has been highlighted as a key cytokine involved in the mechanisms aimed to orchestrate tolerance and has been suggested as a candidate gene in atopic diseases. In this report, we investigate the putative role of TGF-β1 in the regulation of FcεRI on cord blood CD34+ stem cell-derived CD1a+ DC (CD34-derived CD1a + DC). Kinetic experiments show that FcεRI spontaneously appears on the surface of CD1a+ DC, but decreases when exogenous TGF-β1 is added at high doses (10 ng per mL) or when endogenous TGF-β1 is neutralized in the culture conditions. In contrast, low-dose TGF-β1 (0.5 ng per mL) stabilizes surface FcεRI expression on DC. Increasing TGF-β1 concentrations leads to the generation of LC-like DC showing an augmentation in stimulatory capacity towards allogeneic T cells. In view of these data, a picture emerges that FcεRI+ on DC is finely modified by the TGF-β1 concentration in the microenvironrnent and could be of primary relevance in the context of atopic diseases.