PMID- 19164127
OWN - NLM
STAT- MEDLINE
DCOM- 20090424
LR  - 20201226
IS  - 1938-3673 (Electronic)
IS  - 0741-5400 (Linking)
VI  - 85
IP  - 4
DP  - 2009 Apr
TI  - TLR7 and TLR8 agonists trigger different signaling pathways for human dendritic 
      cell maturation.
PG  - 673-83
LID - 10.1189/jlb.0808504 [doi]
AB  - Dendritic cells (DCs) play an important role in bridging innate and adaptive 
      immunity. These APCs have the ability to recognize specific molecular signatures 
      of pathogens through TLRs. In particular, the intracellular TLR7 and TLR8, 
      mediating the recognition of ssRNA by DCs, play a major role in the immune 
      response during viral infection. Although differences have been identified 
      between TLR7 and TLR8, in terms of cellular expression and functions, the 
      signaling pathways that lead to DC maturation following TLR7 or TLR8 engagement 
      are largely unknown. We compared the signaling pathways involved in human CD34-DC 
      maturation induced by agonists selective for TLR7 (imiquimod) or TLR8 (3M002). 
      TLR7 and TLR8 activation up-regulated CCR7, CD40, CD86, and CD83 expression and 
      IL-6 and IL-12p40 production. However, only TLR8 activation led to IL-12p70 
      production and il-12p35 mRNA expression. We found that upon TLR7 and TLR8 
      activation, JNK and NF-kappaB positively regulated the expression of CCR7, CD86, 
      CD83, and CD40 and the production of IL-6 and IL-12p40. However, although p38MAPK 
      participated in the up-regulation of maturation markers in response to TLR7 
      activation, this kinase exerted an inhibitory effect on CD40 expression and IL-12 
      production in TLR8-stimulated DCs. We also showed that the Jak/STAT signaling 
      pathway was involved in CD40 expression and cytokine production in 
      TLR7-stimulated DCs but negatively regulated CD83 expression and cytokine 
      secretion in DCs activated through TLR8. This study showed that TLR7 and TLR8 
      activate similar signaling pathways that play different roles in DC maturation, 
      depending on which TLR is triggered.
FAU - Larange, Alexandre
AU  - Larange A
AD  - Universite Paris-Sud 11, INSERM UMR-S 749, Faculte de Pharmacie, 92296 
      Chatenay-Malabry, France.
FAU - Antonios, Diane
AU  - Antonios D
FAU - Pallardy, Marc
AU  - Pallardy M
FAU - Kerdine-Romer, Saadia
AU  - Kerdine-Romer S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090121
PL  - England
TA  - J Leukoc Biol
JT  - Journal of leukocyte biology
JID - 8405628
RN  - 0 (Antigens, CD)
RN  - 0 (Interleukins)
RN  - 0 (Receptors, Chemokine)
RN  - 0 (Toll-Like Receptor 7)
RN  - 0 (Toll-Like Receptor 8)
RN  - EC 2.7.- (Protein Kinases)
SB  - IM
MH  - Antigens, CD
MH  - Dendritic Cells/*cytology/metabolism
MH  - Humans
MH  - Interleukins
MH  - Protein Kinases
MH  - Receptors, Chemokine
MH  - Signal Transduction/*immunology
MH  - Toll-Like Receptor 7/*agonists
MH  - Toll-Like Receptor 8/*agonists
MH  - Up-Regulation/immunology
EDAT- 2009/01/24 09:00
MHDA- 2009/04/25 09:00
CRDT- 2009/01/24 09:00
PHST- 2009/01/24 09:00 [entrez]
PHST- 2009/01/24 09:00 [pubmed]
PHST- 2009/04/25 09:00 [medline]
AID - jlb.0808504 [pii]
AID - 10.1189/jlb.0808504 [doi]
PST - ppublish
SO  - J Leukoc Biol. 2009 Apr;85(4):673-83. doi: 10.1189/jlb.0808504. Epub 2009 Jan 21.