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The Journal of Immunology, 2000, 164: 1855-1861.
Copyright © 2000 by The American Association of Immunologists

Transcription Factor PU.1 Is Necessary for Development of Thymic and Myeloid Progenitor-Derived Dendritic Cells1

Karen L. Anderson*, Hugh Perkin*, Charles D. Surh*, Sara Venturini*, Richard A. Maki{dagger} and Bruce E. Torbett2,*

* Departments of Molecular and Experimental Medicine and Immunology, Scripps Research Institute, La Jolla, CA 92037; and {dagger} The Burnham Institute, La Jolla, CA 92037

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.




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