Distinct signals control the hematopoiesis of lymphoid-related dendritic cells

The molecular and cellular requirements for the development of different po pulations of human dendritic cells (DC) were studied. Conditions were defin ed that support DC production from lymphoid progenitors but that fail to in duce DC formation from peripheral monocytes. The production of these lympho id-related DC was severely blocked when hematopoietic progenitors overexpre ssed Ik7, a mutant dominant-negative Ikaros protein. In contrast, Ik7 did n ot block the formation of DC in conditions supporting the development of mo nocyte-derived DC. Furthermore, Ik7 did not block the formation of monocyte /macrophages and enhanced granulopoiesis. One of the molecular mechanisms m ediated by Ik7 appears to be down-regulation of the flt3-receptor mRNA, Thu s, distinct signals control the formation of DC demonstrating that some asp ects of DC diversity are determined in part by distinct molecular cues at t he hematopoietic level. (C) 2000 by The American Society of Hematology.