PMID- 22396536
OWN - NLM
STAT- MEDLINE
DCOM- 20120717
LR  - 20211021
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 287
IP  - 17
DP  - 2012 Apr 20
TI  - Activated apoptotic cells induce dendritic cell maturation via engagement of 
      Toll-like receptor 4 (TLR4), dendritic cell-specific intercellular adhesion 
      molecule 3 (ICAM-3)-grabbing nonintegrin (DC-SIGN), and beta2 integrins.
PG  - 13731-42
LID - 10.1074/jbc.M111.336545 [doi]
AB  - Dendritic cells (DCs) are professional antigen-presenting cells playing a central 
      role in connecting innate and adaptive immunity. Maturation signals are, however, 
      required for DCs to undergo phenotypic and functional changes to acquire a fully 
      competent antigen-presenting capacity. We previously reported that activated 
      apoptotic peripheral lymphocytes (ActApo) provide activation/maturation signals 
      to human monocyte-derived DCs. In this paper, we have characterized the signaling 
      pathways and molecules involved in ActApo-mediated DC maturation. We found that 
      both cellular and supernatant fractions from ActApo are required for DC 
      maturation signaling. ActApoSup-induced CD80 and CD86 expression was 
      significantly blocked in the presence of neutralizing antibodies against tumor 
      necrosis factor-alpha (TNF-alpha). Cell-cell contact-dependent signaling involved beta2 
      integrins, dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN), and 
      TLR4 because ActApo-induced up-regulation of the maturation markers CD80 and CD86 
      was significantly inhibited in the presence of neutralizing antibodies against 
      CD18, CD11a, CD11b, and DC-SIGN as well as TLR4. The role of TLR4 was further 
      confirmed by silencing of TLR4 in DCs. In addition, the endogenous adjuvant 
      effect exerted by activated apoptotic splenocytes (ActApoSp) was reduced after 
      immunization with human serum albumin in TLR4(-/-) mice. We detected activation 
      of multiple signaling pathways and transcription factors in DCs upon co-culture 
      with ActApo, including p38, JNK, PI3K-Akt, Src family kinases, NFkappaB p65, and AP1 
      transcription factor family members c-Jun and c-Fos, demonstrating the complex 
      interactions occurring between ActApo and DCs. These studies provide important 
      mechanistic insight into the responses of DCs during encounter with cells 
      undergoing immunogenic cell death.
FAU - Pathak, Sushil Kumar
AU  - Pathak SK
AD  - Department of Medicine, Center for Infectious Medicine, Karolinska Institutet, 
      Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden.
FAU - Skold, Annette E
AU  - Skold AE
FAU - Mohanram, Venkatramanan
AU  - Mohanram V
FAU - Persson, Catrine
AU  - Persson C
FAU - Johansson, Ulrika
AU  - Johansson U
FAU - Spetz, Anna-Lena
AU  - Spetz AL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120306
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Antigens, CD)
RN  - 0 (CD18 Antigens)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (DC-specific ICAM-3 grabbing nonintegrin)
RN  - 0 (ICAM3 protein, human)
RN  - 0 (ICAM3 protein, mouse)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Lipopolysaccharide Receptors)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Animals
MH  - Antigens, CD/*metabolism
MH  - *Apoptosis
MH  - CD18 Antigens/*metabolism
MH  - Cell Adhesion Molecules/*metabolism
MH  - Cell Differentiation
MH  - Coculture Techniques
MH  - Dendritic Cells/*cytology
MH  - Humans
MH  - Lectins, C-Type/*metabolism
MH  - Leukocytes, Mononuclear/cytology
MH  - Lipopolysaccharide Receptors/biosynthesis
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Monocytes/*cytology
MH  - Phenotype
MH  - Receptors, Cell Surface/*metabolism
MH  - Signal Transduction
MH  - Toll-Like Receptor 4/*metabolism
MH  - Transcription Factors/metabolism
PMC - PMC3340136
EDAT- 2012/03/08 06:00
MHDA- 2012/07/18 06:00
PMCR- 2013/04/20
CRDT- 2012/03/08 06:00
PHST- 2012/03/08 06:00 [entrez]
PHST- 2012/03/08 06:00 [pubmed]
PHST- 2012/07/18 06:00 [medline]
PHST- 2013/04/20 00:00 [pmc-release]
AID - S0021-9258(20)52946-3 [pii]
AID - M111.336545 [pii]
AID - 10.1074/jbc.M111.336545 [doi]
PST - ppublish
SO  - J Biol Chem. 2012 Apr 20;287(17):13731-42. doi: 10.1074/jbc.M111.336545. Epub 
      2012 Mar 6.