Stem cell factor plays a key role in the development of human mast cells via interaction with Kit receptor. We and other groups have previously shown that a number of cytokines can regulate the stem-cell-factor-dependent development of mast cells in vitro. In this study we investigated the e¡ect of retinoic acid on human mast cells in vitro and in vivo. Retinoids are known to have strong modulatory e¡ects on hematopoietic di¡erentiation. We found that all-trans-retinoic acid, at concentrations

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... s low as 1 nM, inhibits the stemcell-factor-dependent di¡erentiation of mast cells in vitro. This e¡ect of retinoic acid was found to be on progenitor cells, whereas more mature mast cells were less a¡ected. The use of speci¢c agonists binding either to the RAR or the RXR nuclear receptors indicated involvement of both the RAR/RXR and RXR/RXR pathways in inhibiting mast cell di¡erentiation. In contrast to the e¡ects on mast cell progenitors, retinoic acid had no e¡ect on the number of mature mast cells in skin organ cultures. Furthermore, topical treatment of normal skin with a retinoic-acid-containing cream caused an increase in the number of tryptase-positive mast cells, whereas the numbers of the major cutaneous mast cell type, tryptase-and chymase-positive mast cells, remained una¡ected. Our results suggest that retinoic acid suppresses commitment of progenitor cells into the mast cell lineage and/or acts on early mast cell progenitors, whereas mature cutaneous mast cells are less susceptible to retinoic acid.