Retinoic acid selectively inhibits il-5 receptor expression during progenitor cell differentiation

Retinoids, a class of compounds related to vitamin A, have profound effects on hematopoiesis. We have previously shown that all-trans retinoic acid (ATRA) inhibits eosinophil-basophil differentiation but not neutrophil differentiation in vitro. Whether this effect is mediated through the interleukin-5 receptor (IL-5R) or through another mechanism remains unclear. Hence, we examined the effect of ATRA (10s to 1Q-8M) on purified CD34+ cord blood progenitor cells following short term culture with IL-3, IL-5 and GM-CSF. After seven days, cells were stained with monoclonal antibodies specific for the chains of IL-5R and GM-CSFR, and analyzed by flow cytometry. ATRA exhibited dose dependent inhibition of IL-5R expression, reducing both the percentage of positively staining cells and the intensity of receptor expression. In contrast, ATRA had no significant effect on GM-CSFR expression. These effects were observed regardless of whether ATRA was present throughout the culture period, or only for the initial three days. Thus, we hypothesize that ATRA acts at a very early stage of eosinophil differentiation to selectively inhibit IL-5R expression. Moreover, these findings raise interesting issues concerning the physiological regulation of the IL-5R, and suggest that retinoids should be examined further for their capacity to modify eosinophil differentiation in animal models of allergic inflammation.