PMID- 19667404
OWN - NLM
STAT- MEDLINE
DCOM- 20091027
LR  - 20211020
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 114
IP  - 15
DP  - 2009 Oct 8
TI  - A novel role for c-Src and STAT3 in apoptotic cell-mediated MerTK-dependent 
      immunoregulation of dendritic cells.
PG  - 3191-8
LID - 10.1182/blood-2009-03-207522 [doi]
AB  - Dendritic cells (DCs) play an instrumental role in regulating tolerance to 
      self-antigens and preventing autoimmunity. One mechanism by which "tolerogenic" 
      DCs are established is through the inhibitory effects of apoptotic cells (ACs). 
      Immature DCs encountering ACs are resistant to stimuli that activate and mature 
      DCs. We have shown that the Mer receptor tyrosine kinase (MerTK) plays a key role 
      in transducing inhibitory signals upon binding of ACs, which in turn involve the 
      phosphatidylinositol 3-kinase (PI3K) pathway. Nevertheless, the molecular basis 
      for AC-induced inhibition of DCs is ill defined. In the current study, the 
      proximal signaling events induced by MerTK after AC binding were studied. AC 
      treatment of bone marrow-derived or splenic DCs established a complex consisting 
      of MerTK, the nonreceptor tyrosine kinase c-Src, the transcription factor STAT3, 
      and PI3K. In contrast, AC treatment of DCs lacking MerTK expression failed to 
      increase c-Src and STAT3 activation. In addition, the inhibitory effects of ACs 
      were blocked by treating DCs with pharmacologic inhibitors or siRNA specific for 
      c-Src and STAT3. These findings demonstrate that AC-induced inhibition of DCs 
      requires MerTK-dependent activation of c-Src and STAT3, and provide evidence for 
      novel roles for c-Src and STAT3 in the immunoregulation of DCs.
FAU - Yi, Zuoan
AU  - Yi Z
AD  - Department of Microbiology and Immunology, University of North Carolina at Chapel 
      Hill, Chapel Hill, NC 27599-7290, USA.
FAU - Li, Li
AU  - Li L
FAU - Matsushima, Glenn K
AU  - Matsushima GK
FAU - Earp, H Shelton
AU  - Earp HS
FAU - Wang, Bo
AU  - Wang B
FAU - Tisch, Roland
AU  - Tisch R
LA  - eng
GR  - R01 AI066075/AI/NIAID NIH HHS/United States
GR  - AI066075/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 - 20090810
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Stat3 protein, mouse)
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)
RN  - EC 2.7.10.2 (src-Family Kinases)
SB  - IM
MH  - Animals
MH  - Apoptosis/genetics/*immunology
MH  - Bone Marrow Cells/immunology/metabolism
MH  - Dendritic Cells/*immunology/metabolism
MH  - Female
MH  - *Immune Tolerance
MH  - Male
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, Knockout
MH  - Phosphatidylinositol 3-Kinases/genetics/immunology/metabolism
MH  - Proto-Oncogene Proteins/genetics/*immunology/metabolism
MH  - Receptor Protein-Tyrosine Kinases/genetics/*immunology/metabolism
MH  - STAT3 Transcription Factor/genetics/*immunology/metabolism
MH  - Signal Transduction/genetics/immunology
MH  - c-Mer Tyrosine Kinase
MH  - src-Family Kinases/genetics/*immunology/metabolism
PMC - PMC2759647
EDAT- 2009/08/12 09:00
MHDA- 2009/10/29 06:00
PMCR- 2010/10/08
CRDT- 2009/08/12 09:00
PHST- 2009/08/12 09:00 [entrez]
PHST- 2009/08/12 09:00 [pubmed]
PHST- 2009/10/29 06:00 [medline]
PHST- 2010/10/08 00:00 [pmc-release]
AID - S0006-4971(20)36794-X [pii]
AID - 2009/207522 [pii]
AID - 10.1182/blood-2009-03-207522 [doi]
PST - ppublish
SO  - Blood. 2009 Oct 8;114(15):3191-8. doi: 10.1182/blood-2009-03-207522. Epub 2009 
      Aug 10.