PMID- 20421650
OWN - NLM
STAT- MEDLINE
DCOM- 20100614
LR  - 20150813
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 184
IP  - 11
DP  - 2010 Jun 1
TI  - Transcription factor E2F1 suppresses dendritic cell maturation.
PG  - 6084-91
LID - 10.4049/jimmunol.0902561 [doi]
AB  - Transcription factor E2F1 has been largely studied as a promoter of S-phase 
      transition in the cell cycle and as a regulator of apoptosis. Recently, E2F1 has 
      been shown to regulate a wide range of genes in response to inflammatory 
      stimulation of macrophages and to contribute to T cell activation in response to 
      pathogens, implicating an extensive immunological role for E2F1. Dendritic cells 
      (DCs) play critical roles as professional APCs in the development of immune 
      responses. However, it is unclear whether E2F1 has any effect on DC phenotype or 
      function. In this paper, we report that E2F1 acts as a suppressor of DC 
      maturation. The level of E2F1 expression was transiently downregulated in the 
      course of LPS-induced maturation of both human monocyte-derived DCs and a mouse 
      DC cell line, DC2.4. Knockdown of E2F1 by small interfering RNA in DC2.4 cells 
      resulted in both phenotypic and functional maturation, even without LPS 
      treatment. Conversely, ectopic overexpression of E2F1 suppressed LPS-induced 
      maturation of DC2.4 cells. Furthermore, knockdown of E2F1 caused the activation 
      of several major signaling pathways known to be activated in the course of DC 
      maturation, including Erk1/2, NF-kappaB, and PI3K/Akt, suggesting that E2F1 may 
      be involved in regulating multiple signaling pathways in DCs. Finally, the 
      alteration of phenotypic maturation by E2F1 was confirmed with bone 
      marrow-derived DCs from E2F1 knockout mice. Overall, our data demonstrate for the 
      first time that E2F1 is a critical regulator of DC maturation.
FAU - Fang, Fang
AU  - Fang F
AD  - Hefei National Laboratory for Physical Sciences at Microscale and School of Life 
      Sciences, University of Science and Technology of China, Hefei, China.
FAU - Wang, Yan
AU  - Wang Y
FAU - Li, Rui
AU  - Li R
FAU - Zhao, Ying
AU  - Zhao Y
FAU - Guo, Yang
AU  - Guo Y
FAU - Jiang, Ming
AU  - Jiang M
FAU - Sun, Jie
AU  - Sun J
FAU - Ma, Yang
AU  - Ma Y
FAU - Ren, Zijia
AU  - Ren Z
FAU - Tian, Zhigang
AU  - Tian Z
FAU - Wei, Feng
AU  - Wei F
FAU - Yang, De
AU  - Yang D
FAU - Xiao, Weihua
AU  - Xiao W
LA  - eng
GR  - N01-CO-12400/CO/NCI NIH HHS/United States
GR  - Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100426
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (E2F1 Transcription Factor)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cell Differentiation/*immunology
MH  - Cell Line
MH  - Cell Separation
MH  - Dendritic Cells/*cytology/immunology/metabolism
MH  - E2F1 Transcription Factor/*immunology/metabolism
MH  - Flow Cytometry
MH  - Humans
MH  - Mice
MH  - Mice, Knockout
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transfection
EDAT- 2010/04/28 06:00
MHDA- 2010/06/15 06:00
CRDT- 2010/04/28 06:00
PHST- 2010/04/28 06:00 [entrez]
PHST- 2010/04/28 06:00 [pubmed]
PHST- 2010/06/15 06:00 [medline]
AID - jimmunol.0902561 [pii]
AID - 10.4049/jimmunol.0902561 [doi]
PST - ppublish
SO  - J Immunol. 2010 Jun 1;184(11):6084-91. doi: 10.4049/jimmunol.0902561. Epub 2010 
      Apr 26.