PU.1 is required for myeloid-derived but not lymphoid-derived dendritic cells.
The ets-family transcription factor PU.1 is required for the proper development of both myeloid and lymphoid progenitors. We used PU. 1-deficient animals to examine the role of PU.1 during dendritic cell development. PU.1(-/-)animals produce lymphoid-derived dendritic cells (DC): low-density class II major histocompatibility complex [MHC-II(+)] CD11c(+) CD8alpha(+) DEC-205(+). But they lack myeloid-derived DC: low-density MHC-II(+) CD11c(+) CD8alpha(-) DEC-205(-). PU.1(-/-) embryos also lack progenitors capable of differentiating into myeloid DC in response to granulocyte-macrophage colony-stimulating factor plus interleukin-4. The appearance of lymphoid DC in developing PU.1(-/-)thymus was initially delayed, but this population recovered to wild type (WT) levels upon organ culture of isolated thymic lobes. PU. 1(-/-)lymphoid DC were functionally equivalent to WT DC for stimulating T-cell proliferation in mixed lymphocyte reactions. These results demonstrate that PU.1 is required for the development of myeloid DC but not lymphoid DC.
Guerriero
A
A
Institute for Human Gene Therapy, University of Pennsylvania, Philadelphia, PA 19104-6140, USA.
Langmuir
P B
PB
Spain
L M
LM
Scott
E W
EW
D000818:Animals; D017951:Antigen Presentation; D001853:Bone Marrow / Q000196:embryology; D001854:Bone Marrow Cells / Q000166:cytology; D019070:Cell Lineage; D017637:Clonal Deletion; D003713:Dendritic Cells / Q000145:classification / Q000166:cytology* / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006410:Hematopoiesis / Q000187:drug effects / Q000235:genetics; D016130:Immunophenotyping; D015847:Interleukin-4 / Q000494:pharmacology; D008221:Lymphoid Tissue / Q000166:cytology / Q000196:embryology; D051379:Mice; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology / Q000196:embryology; D015534:Trans-Activators / Q000187:drug effects / Q000502:physiology*; D000099232:Proto-Oncogene Protein Spi-1
D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D015847:Interleukin-4; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1