Transcription factor PU.1 is necessary for development of thymic and myeloid progenitor-derived dendritic cells

Dendritic cells (DCs) are a heterogeneous population of cells that are spec ialized for Ag processing and presentation. These cells are believed to der ive from both myeloid- and lymphoid-committed precursors. Normal human PBMC -derived, human CD14(+) cell (monocyte)-derived, and mouse hematopoietic pr ogenitor-derived DCs were shown to express the hematopoietic cell-restricte d, ets family transcription factor PU,I, These populations represent myeloi d progenitor-derived DCs. Hematopoietic progenitor cells from PU.1 gene-dis rupted (null) mice were unable to generate MHC class IIhigh, CD11c(+) myelo id-derived DCs in vitro, Mouse thymic DCs are proposed to be derived from a committed lymphoid progenitor cell that can give rise to T cells as well a s DCs, Previously, we showed that CD4 and CD8 T cells developed in PU,1 nul l mice in a delayed manner and in reduced number, We examined the thymus of 10- to 12-day-old PU.1 null mice and found no evidence of DEC-205(+), MTDC -8(+) DCs in this tissue, Our findings indicate that PU.1 regulates the dev elopment of both thymic and myeloid progenitor-derived populations of Des, and expand its known role in hematopoietic development.