Distinct signals control the hematopoiesis of lymphoid-related dendritic cells.
The molecular and cellular requirements for the development of different populations of human dendritic cells (DC) were studied. Conditions were defined that support DC production from lymphoid progenitors but that fail to induce DC formation from peripheral monocytes. The production of these lymphoid-related DC was severely blocked when hematopoietic progenitors overexpressed Ik7, a mutant dominant-negative Ikaros protein. In contrast, Ik7 did not block the formation of DC in conditions supporting the development of monocyte-derived DC. Furthermore, Ik7 did not block the formation of monocyte/macrophages and enhanced granulopoiesis. One of the molecular mechanisms mediated by Ik7 appears to be down-regulation of the flt3-receptor mRNA. Thus, distinct signals control the formation of DC demonstrating that some aspects of DC diversity are determined in part by distinct molecular cues at the hematopoietic level. (Blood. 2000;95:128-137)
Galy
A
A
Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA. galya@kci.wayne.edu
Christopherson
I
I
Ferlazzo
G
G
Liu
G
G
Spits
H
H
Georgopoulos
K
K
D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D004268:DNA-Binding Proteins; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D015536:Down-Regulation; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006410:Hematopoiesis / Q000187:drug effects / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D051740:Ikaros Transcription Factor; D007378:Interleukins / Q000494:pharmacology; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008264:Macrophages / Q000166:cytology; D009000:Monocytes / Q000166:cytology; D015260:Neprilysin / Q000032:analysis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D019089:Stem Cell Factor / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D016335:Zinc Fingers; D051941:fms-Like Tyrosine Kinase 3
D015703:Antigens, CD; D018952:Antigens, CD34; D016207:Cytokines; D004268:DNA-Binding Proteins; C497239:IKZF1 protein, human; D007378:Interleukins; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D051740:Ikaros Transcription Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C497970:FLT3 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3; D015260:Neprilysin