Analysis of transcription factors in thymic and CD34+ progenitor-derived plasmacytoid and myeloid dendritic cells: evidence for distinct expression profiles.
OBJECTIVE
The expression of mRNA for pre-Talpha is specific for human plasmacytoid dendritic cells (PDC), a population ontogenically close to T cells. The latter need Gata-3 transcription factor to develop. PU1 and RelB are two transcription factors involved in the development of murine myeloid DC (MDC). To determine the lineage origin of human thymic DC, the expression of these genes was investigated.


METHODS
Fresh thymic DC, CD34(+)CD1a(-) progenitors, and progenitor-derived DC populations were sorted, analyzed, and compared to blood DC.


RESULTS
Three DC populations were found in the thymus. 1) CD123(-/lo)HLA-DR(hi) DC expressing PU1 and RelB; 2) CD123(hi)HLA-DR(+) DC expressing only pre-Talpha, the expression of which was similar to that of MDC and PDC from peripheral blood; and 3) a new mature CD123(hi)HLA-DR(hi) PDC population with pre-Talpha, PU1 and RelB mRNAs. In culture, most CD34(+)CD1a(-) progenitors remained CD1a(-)CD123(-); had a T and natural killer cell differentiation potential; and expressed Gata-3 mRNA contrary to DC precursors. A few cells (10%) became CD1a(+)CD123(+) expressing pre-Talpha, PU1, and RelB mRNAs and were able to differentiate into typical Langerhans cells with transforming growth factor-beta. Coculture of thymic progenitors on a murine cell line generated CD123(hi)CD1a(-) cells with typical PDC morphology, expressing pre-Talpha but not PU1 and RelB transcripts. Activated PDC acquired myeloid antigens, and up-regulated PU1 and RelB mRNAs while down-regulating pre-Talpha mRNA expression.


CONCLUSIONS
Both DC maturation pathways may arise from distinct precursors but are interconnected. DC differentiation seems to occur from Gata-3(-) precursors upstream of T and natural killer precursors.
Fohrer
Hélène
H
INSERM U543, Hôpital Pitié-Salpêtrière, Paris, France.
Audit
Isabelle Max
IM
Sainz
Alexandre
A
Schmitt
Christian
C
Dezutter-Dambuyant
Colette
C
Dalloul
Ali H
AH
D018949:Antigens, CD1 / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis*; D002454:Cell Differentiation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics; D003713:Dendritic Cells / Q000378:metabolism*; D050990:GATA3 Transcription Factor; D020869:Gene Expression Profiling; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D050835:Interferon Regulatory Factors; D053650:Interleukin-3 Receptor alpha Subunit; D008562:Membrane Glycoproteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016185:Receptors, Interleukin-3 / Q000032:analysis; D013950:Thymus Gland / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics; D051841:Transcription Factor RelB; D014157:Transcription Factors / Q000235:genetics*; D000099218:Interferon Regulatory Factor-4
D018949:Antigens, CD1; D018952:Antigens, CD34; D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; D050835:Interferon Regulatory Factors; D053650:Interleukin-3 Receptor alpha Subunit; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016185:Receptors, Interleukin-3; D015534:Trans-Activators; D051841:Transcription Factor RelB; D014157:Transcription Factors; D000099218:Interferon Regulatory Factor-4; C419393:CD1a antigen; C494749:GATA3 protein, human; C115022:IL3RA protein, human; C497593:RELB protein, human; C090377:pre-T cell receptor alpha