PMID- 16896155
OWN - NLM
STAT- MEDLINE
DCOM- 20070117
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 108
IP  - 13
DP  - 2006 Dec 15
TI  - Involvement of suppressors of cytokine signaling in toll-like receptor-mediated 
      block of dendritic cell differentiation.
PG  - 4102-8
AB  - Dendritic cells (DCs) are important sentinels within innate immunity, monitoring 
      the presence of infectious microorganisms. They operate in 2 different maturation 
      stages, with transition from immature to mature DCs being induced by activation 
      of toll-like receptors (TLRs). However, TLRs are also expressed on precursor 
      cells of DCs. Here we analyzed the effects of TLR stimulation during the process 
      of granulocyte-macrophage-colony-stimulating factor (GM-CSF)-mediated in vitro 
      generation of immature DCs from precursor cells. We show that TLR triggering 
      deviated phenotypic and functional differentiation from CD14+ monocytes to CD1a+ 
      DCs. Similar results were obtained when differentiation of murine myeloid DCs 
      from bone marrow cells was analyzed. The inhibitory effects were independent of 
      soluble factors. TLR stimulation in DC precursor cells induced proteins of the 
      suppressor of cytokine signaling family (SOCS), which correlated with loss of 
      sensitivity to GM-CSF. Overexpression of SOCS-1 abolished GM-CSF signal 
      transduction. Moreover, forced SOCS-1 expression in DC precursors mimicked the 
      inhibitory effects on DC generation observed for TLR stimulation. The results 
      indicate that TLR stimulation during the period of DC generation interferes with 
      and deviates DC differentiation and that these effects are mediated particularly 
      by SOCS-1.
FAU - Bartz, Holger
AU  - Bartz H
AD  - Department of Medical Microbiology and Hygiene, Hygiene Institute, University of 
      Heidelberg, Im Neuenheimer Feld 324, D-69120 Heidelberg, Germany. 
      holger.bartz@med.uni-heidelberg.de
FAU - Avalos, Nicole M
AU  - Avalos NM
FAU - Baetz, Andrea
AU  - Baetz A
FAU - Heeg, Klaus
AU  - Heeg K
FAU - Dalpke, Alexander H
AU  - Dalpke AH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060808
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antigens, CD1)
RN  - 0 (CD1a antigen)
RN  - 0 (Lipopolysaccharide Receptors)
RN  - 0 (Socs1 protein, mouse)
RN  - 0 (Suppressor of Cytokine Signaling 1 Protein)
RN  - 0 (Suppressor of Cytokine Signaling Proteins)
RN  - 0 (Toll-Like Receptors)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
SB  - IM
MH  - Animals
MH  - Antigens, CD1/immunology
MH  - Bone Marrow Cells/immunology
MH  - Cell Differentiation/drug effects/*immunology
MH  - Cells, Cultured
MH  - Dendritic Cells/*immunology
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/*immunology/pharmacology
MH  - Immunity, Innate/immunology
MH  - Lipopolysaccharide Receptors/immunology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Knockout
MH  - Monocytes/immunology
MH  - Signal Transduction/drug effects/*immunology
MH  - Suppressor of Cytokine Signaling 1 Protein
MH  - Suppressor of Cytokine Signaling Proteins/*immunology
MH  - Toll-Like Receptors/deficiency/*immunology
EDAT- 2006/08/10 09:00
MHDA- 2007/01/18 09:00
CRDT- 2006/08/10 09:00
PHST- 2006/08/10 09:00 [pubmed]
PHST- 2007/01/18 09:00 [medline]
PHST- 2006/08/10 09:00 [entrez]
AID - S0006-4971(20)52207-6 [pii]
AID - 10.1182/blood-2006-03-008946 [doi]
PST - ppublish
SO  - Blood. 2006 Dec 15;108(13):4102-8. doi: 10.1182/blood-2006-03-008946. Epub 2006 
      Aug 8.