PMID- 17008547
OWN - NLM
STAT- MEDLINE
DCOM- 20070830
LR  - 20220311
IS  - 0006-4971 (Print)
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 109
IP  - 2
DP  - 2007 Jan 15
TI  - Apoptotic cells induce Mer tyrosine kinase-dependent blockade of NF-kappaB 
      activation in dendritic cells.
PG  - 653-60
AB  - Dendritic cells (DCs) play a key role in immune homeostasis and maintenance of 
      self-tolerance. Tolerogenic DCs can be established by an encounter with apoptotic 
      cells (ACs) and subsequent inhibition of maturation and effector functions. The 
      receptor(s) and signaling pathway(s) involved in AC-induced inhibition of DCs 
      have yet to be defined. We demonstrate that pretreatment with apoptotic but not 
      necrotic cells inhibits activation of IkappaB kinase (IKK) and downstream 
      NF-kappaB. Notably, receptor tyrosine kinase Mer (MerTK) binding of ACs is 
      required for mediating this effect. Monocyte-derived DCs lacking MerTK expression 
      (MerTKKD) or treated with blocking MerTK-specific antibodies (Abs) are resistant 
      to AC-induced inhibition and continue to activate NF-kappaB and secrete 
      proinflammatory cytokines. Blocking MerTK activation of the phosphatidylinositol 
      3-kinase (PI3K)/AKT pathway prevents AC-induced inhibition. These results 
      demonstrate an essential role for MerTK-mediated regulation of the PI3K/AKT and 
      NF-kappaB pathways in AC-induced inhibition of monocyte-derived DCs.
FAU - Sen, Pradip
AU  - Sen P
AD  - Department of Microbiology and Immunology, Mary Ellen Jones Bldg, Rm 804, Campus 
      Box 7290, University of North Carolina Lineberger Comprehensive Cancer Center, 
      Chapel Hill, NC 27599-7290, USA.
FAU - Wallet, Mark A
AU  - Wallet MA
FAU - Yi, Zuoan
AU  - Yi Z
FAU - Huang, Yingsu
AU  - Huang Y
FAU - Henderson, Michael
AU  - Henderson M
FAU - Mathews, Clayton E
AU  - Mathews CE
FAU - Earp, H Shelton
AU  - Earp HS
FAU - Matsushima, Glenn
AU  - Matsushima G
FAU - Baldwin, Albert S Jr
AU  - Baldwin AS Jr
FAU - Tisch, Roland M
AU  - Tisch RM
LA  - eng
GR  - P60 DE013079/DE/NIDCR NIH HHS/United States
GR  - R37 AI035098/AI/NIAID NIH HHS/United States
GR  - AI066075/AI/NIAID NIH HHS/United States
GR  - AI35098/AI/NIAID NIH HHS/United States
GR  - R01 AI050736/AI/NIAID NIH HHS/United States
GR  - R01 AI066075/AI/NIAID NIH HHS/United States
GR  - 1-P60-DE 13079/DE/NIDCR NIH HHS/United States
GR  - U19 AI056374/AI/NIAID NIH HHS/United States
GR  - AI056374/AI/NIAID NIH HHS/United States
GR  - AI50736/AI/NIAID NIH HHS/United States
GR  - R01 AI035098/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20060928
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antibodies)
RN  - 0 (NF-kappa B)
RN  - 0 (Proto-Oncogene Proteins)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.1 (Mertk protein, mouse)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (c-Mer Tyrosine Kinase)
SB  - IM
MH  - Animals
MH  - Antibodies/immunology
MH  - Apoptosis/*immunology
MH  - Cells, Cultured
MH  - Dendritic Cells/*immunology
MH  - Female
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred NOD
MH  - Mice, Knockout
MH  - NF-kappa B/*metabolism
MH  - Phosphatidylinositol 3-Kinases/immunology
MH  - Proto-Oncogene Proteins/*immunology
MH  - Receptor Protein-Tyrosine Kinases/*immunology
MH  - Signal Transduction/immunology
MH  - c-Mer Tyrosine Kinase
PMC - PMC1785106
COIS- Conflict-of-interest disclosure: The authors declare no competing financial 
      interests.
EDAT- 2006/09/30 09:00
MHDA- 2007/08/31 09:00
PMCR- 2008/01/15
CRDT- 2006/09/30 09:00
PHST- 2006/09/30 09:00 [pubmed]
PHST- 2007/08/31 09:00 [medline]
PHST- 2006/09/30 09:00 [entrez]
PHST- 2008/01/15 00:00 [pmc-release]
AID - S0006-4971(20)52076-4 [pii]
AID - 2006/017368 [pii]
AID - 10.1182/blood-2006-04-017368 [doi]
PST - ppublish
SO  - Blood. 2007 Jan 15;109(2):653-60. doi: 10.1182/blood-2006-04-017368. Epub 2006 
      Sep 28.