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(+) CD8 alpha(+) DEC-205(+), But they lack myeloid-derived DC: low-density MHC-II+ CD11c(+) CD8 alpha(-) 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. (C) 2000 by The American Society of Hematology.