Reciprocal roles for CCAAT/enhancer binding protein (C/EBP) and PU.1 transcription factors in Langerhans cell commitment.
Myeloid progenitor cells give rise to a variety of progenies including dendritic cells. However, the mechanism controlling the diversification of myeloid progenitors into each progeny is largely unknown. PU.1 and CCAAT/enhancing binding protein (C/EBP) family transcription factors have been characterized as key regulators for the development and function of the myeloid system. However, the roles of C/EBP transcription factors have not been fully identified because of functional redundancy among family members. Using high titer--retroviral infection, we demonstrate that a dominant-negative C/EBP completely blocked the granulocyte--macrophage commitment of human myeloid progenitors. Alternatively, Langerhans cell (LC) commitment was markedly facilitated in the absence of tumor necrosis factor (TNF)alpha, a strong inducer of LC development, whereas expression of wild-type C/EBP in myeloid progenitors promoted granulocytic differentiation, and completely inhibited TNFalpha-dependent LC development. On the other hand, expression of wild-type PU.1 in myeloid progenitors triggered LC development in the absence of TNFalpha, and its instructive effect was canceled by coexpressed C/EBP. Our findings establish reciprocal roles for C/EBP and PU.1 in LC development, and provide new insight into the molecular mechanism of LC development, which has not yet been well characterized.
Iwama
Atsushi
A
Department of Immunology, Institute of Basic Medical Sciences, Core Research for Evolutional Science and Technology (CREST) Program of Japan Science and Technology (JST). aiwama@md.tsukuba.ac.jp
Osawa
Mitsujiro
M
Hirasawa
Ryutaro
R
Uchiyama
Noriko
N
Kaneko
Shin
S
Onodera
Masafumi
M
Shibuya
Kazuko
K
Shibuya
Akira
A
Vinson
Charles
C
Tenen
Daniel G
DG
Nakauchi
Hiromitsu
H
D022762:CCAAT-Enhancer-Binding Proteins / Q000502:physiology*; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000502:physiology; D006098:Granulocytes / Q000502:physiology; D006801:Humans; D007801:Langerhans Cells / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D015534:Trans-Activators / Q000502:physiology*; D020298:U937 Cells; D000099232:Proto-Oncogene Protein Spi-1
D022762:CCAAT-Enhancer-Binding Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1