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 specialized for Ag processing and presentation. These cells are believed to derive from both myeloid- and lymphoid-committed precursors. Normal human PBMC-derived, human CD14+ cell (monocyte)-derived, and mouse hematopoietic progenitor-derived DCs were shown to express the hematopoietic cell-restricted, ets family transcription factor PU.1. These populations represent myeloid progenitor-derived DCs. Hematopoietic progenitor cells from PU.1 gene-disrupted (null) mice were unable to generate MHC class IIhigh, CD11c+ myeloid-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 as DCs. Previously, we showed that CD4 and CD8 T cells developed in PU.1 null 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+, MIDC-8+ DCs in this tissue. Our findings indicate that PU.1 regulates the development of both thymic and myeloid progenitor-derived populations of DCs, and expand its known role in hematopoietic development.
Anderson
K L
KL
Department of Molecular Medicine, Scripps Research Institute, La Jolla, CA 92037, USA.
Perkin
H
H
Surh
C D
CD
Venturini
S
S
Maki
R A
RA
Torbett
B E
BE
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology / Q000473:pathology; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000099232:Proto-Oncogene Protein Spi-1
D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1