The effects of retinoic acid on the proliferation and cell cycling of myeloid dendritic cells in response to granulocyte-macrophage colony-stimulating factor
All-trans retinoic acid (atRA) carries out most of the biological activities of vitamin A and plays a major role in embryogenesis, cell differentiation and immune functions. Vitamin A favors the differentiation of myeloid progenitors to immature myeloid dendritic cells (DC) instead of granulocytes when vitamin A is adequate in culture, suggesting that vitamin A deficiency may cause changes in adaptive immune responses that depend on myeloid DC antigen presentation. We investigated the effect of atRA on the differentiation of myeloid progenitor cells in response to granulocyte-macrophage colony-stimulating factor (GM-CSF) and cycling of the resultant cell populations. We observed a gradual decline in percent of DC obtained at culture harvest as the addition of vitamin A to the myeloid progenitors was delayed. In addition, mouse bone marrow cells cultured with GM-CSF and treated with 10 nM atRA showed increased cell proliferation. To further investigate the role of vitamin A in DC proliferation, the same concentration of atRA was used and compared to a retinoic acid receptor (RAR)-α antagonist (AGN 194301) to observe differences in cell cycle. Following addition of GM-CSF to DC cultures more cells were in S-phase when treated with atRA compared to AGN 194301. These data suggest that atRA is promoting an increase in the progression of cells from G1 to S-phase of the cell cycle, thereby optimizing myeloid DC proliferation in response to GM-CSF.