PU.1 is required for myeloid-derived but not lymphoid-derived dendritic cells

Abstract

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+DEC-205+. But they lack myeloid-derived DC: low-density MHC-II+ CD11c+ CD8−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.