PMID- 23284905
OWN - NLM
STAT- MEDLINE
DCOM- 20130620
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 12
DP  - 2012
TI  - PU.1 is essential for CD11c expression in CD8(+)/CD8(-) lymphoid and 
      monocyte-derived dendritic cells during GM-CSF or FLT3L-induced differentiation.
PG  - e52141
LID - 10.1371/journal.pone.0052141 [doi]
LID - e52141
AB  - Dendritic cells (DCs) regulate innate and acquired immunity through their roles 
      as antigen-presenting cells. Specific subsets of mature DCs, including 
      monocyte-derived and lymphoid-derived DCs, can be distinguished based on distinct 
      immunophenotypes and functional properties. The leukocyte integrin, CD11c, is 
      considered a specific marker for DCs and it is expressed by all DC subsets. We 
      created a strain of mice in which DCs and their progenitors could be lineage 
      traced based on activity of the CD11c proximal promoter. Surprisingly, we 
      observed levels of CD11c promoter activity that were similar in DCs and in other 
      mature leukocytes, including monocytes, granulocytes, and lymphocytes. We sought 
      to identify DNA elements and transcription factors that regulate DC-associated 
      expression of CD11c. The ets transcription factor, PU.1, is a key regulator of DC 
      development, and expression of PU.1 varies in different DC subsets. GM-CSF 
      increased monocyte-derived DCs in mice and from mouse bone marrow cultured in 
      vitro, but it did not increase CD8(+) lymphoid-derived DCs or B220(+) 
      plasmacytoid DCs. FLT3L increased both monocyte-derived DCs and lymphoid-derived 
      DCs from mouse bone marrow cultured in vitro. GM-CSF increased the 5.3 Kb CD11c 
      proximal promoter activity in monocyte-derived DCs and CD8(+) lymphoid-derived 
      DCs, but not in B220(+) plasmacytoid DCs. In contrast, FLT3L increased the CD11c 
      proximal promoter activity in both monocyte-derived DCs and B220(+) plasmacytoid 
      DCs. We used shRNA gene knockdown and chromatin immunoprecipitation to 
      demonstrate that PU.1 is required for the effects of GM-CSF or FLT3L on 
      monocyte-derived DCs. We conclude that both GM-CSF and FLT3L act through PU.1 to 
      activate the 5.3 Kb CD11c proximal promoter in DCs and to induce differentiation 
      of monocyte-derived DCs. We also confirm that the CD11c proximal promoter is not 
      sufficient to direct lineage specificity of CD11c expression, and that additional 
      DNA elements are required for lineage-specific CD11c expression.
FAU - Zhu, Xue-Jun
AU  - Zhu XJ
AD  - Cell and Molecular Biology Laboratory, Division of Hematology, Department of 
      Medicine, Jiangsu Provincial Traditional Chinese Medical Hospital, Nanjing, 
      China. Zhuxj2@hotmail.com
FAU - Yang, Zhong-Fa
AU  - Yang ZF
FAU - Chen, Yaoyu
AU  - Chen Y
FAU - Wang, Junling
AU  - Wang J
FAU - Rosmarin, Alan G
AU  - Rosmarin AG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121220
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (CD11c Antigen)
RN  - 0 (Membrane Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (flt3 ligand protein)
RN  - 0 (proto-oncogene protein Spi-1)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
SB  - IM
MH  - Animals
MH  - CD11c Antigen/genetics/*metabolism
MH  - CD8-Positive T-Lymphocytes/drug effects/metabolism
MH  - Cell Differentiation/drug effects
MH  - Cells, Cultured
MH  - Chromatin Immunoprecipitation
MH  - Dendritic Cells/*drug effects/*metabolism
MH  - Flow Cytometry
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/*pharmacology
MH  - Immunoblotting
MH  - Membrane Proteins/*pharmacology
MH  - Mice
MH  - Monocytes/*cytology
MH  - Polymerase Chain Reaction
MH  - Proto-Oncogene Proteins/genetics/*metabolism
MH  - Trans-Activators/genetics/*metabolism
PMC - PMC3527425
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/01/04 06:00
MHDA- 2013/06/21 06:00
PMCR- 2012/12/20
CRDT- 2013/01/04 06:00
PHST- 2012/08/16 00:00 [received]
PHST- 2012/11/08 00:00 [accepted]
PHST- 2013/01/04 06:00 [entrez]
PHST- 2013/01/04 06:00 [pubmed]
PHST- 2013/06/21 06:00 [medline]
PHST- 2012/12/20 00:00 [pmc-release]
AID - PONE-D-12-24538 [pii]
AID - 10.1371/journal.pone.0052141 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(12):e52141. doi: 10.1371/journal.pone.0052141. Epub 2012 Dec 20.