PMID- 15356132
OWN - NLM
STAT- MEDLINE
DCOM- 20041019
LR  - 20220408
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 173
IP  - 6
DP  - 2004 Sep 15
TI  - IL-6 regulates in vivo dendritic cell differentiation through STAT3 activation.
PG  - 3844-54
AB  - Dendritic cells (DCs) orchestrate immune responses according to their state of 
      maturation. In response to infection, DCs differentiate into mature cells that 
      initiate immune responses, while in the absence of infection, most of them remain 
      in an immature form that induces tolerance to self Ags. Understanding what 
      controls these opposing effects is an important goal for vaccine development and 
      prevention of unwanted immune responses. A crucial question is what cytokine(s) 
      regulates DC maturation in the absence of infection. In this study, we show that 
      IL-6 plays a major role in maintaining immature DCs. IL-6 knockout (KO) mice had 
      increased numbers of mature DCs, indicating that IL-6 blocks DC maturation in 
      vivo. We examined this effect further in knockin mice expressing mutant versions 
      of the IL-6 signal transducer gp130, with defective signaling through either Src 
      homology region 2 domain-containing phosphatase 2/Gab/MAPK (gp130(F759/F759)) or 
      STAT3 (gp130(FxxQ/FxxQ)), and combined gp130 and IL-6 defects 
      (gp130(F759/F759)/IL-6 KO mice). Importantly, we found STAT3 activation by IL-6 
      was required for the suppression of LPS-induced DC maturation. In addition, STAT3 
      phosphorylation in DCs was regulated by IL-6 in vivo, and STAT3 was necessary for 
      the IL-6 suppression of bone marrow-derived DC activation/maturation. DC-mediated 
      T cell activation was enhanced in IL-6 KO mice and suppressed in gp130(F759/F759) 
      mice. IL-6 is thus a potent regulator of DC differentiation in vivo, and 
      IL-6-gp130-STAT3 signaling in DCs may represent a critical target for controlling 
      T cell-mediated immune responses in vivo.
CI  - Copyright 2004 The American Association of Immunologists, Inc.
FAU - Park, Sung-Joo
AU  - Park SJ
AD  - Department of Molecular Oncology, Graduate School of Medicine, Osaka University, 
      Suita, Japan.
FAU - Nakagawa, Takayuki
AU  - Nakagawa T
FAU - Kitamura, Hidemitsu
AU  - Kitamura H
FAU - Atsumi, Toru
AU  - Atsumi T
FAU - Kamon, Hokuto
AU  - Kamon H
FAU - Sawa, Shin-Ichiro
AU  - Sawa S
FAU - Kamimura, Daisuke
AU  - Kamimura D
FAU - Ueda, Naoko
AU  - Ueda N
FAU - Iwakura, Yoichiro
AU  - Iwakura Y
FAU - Ishihara, Katsuhiko
AU  - Ishihara K
FAU - Murakami, Masaaki
AU  - Murakami M
FAU - Hirano, Toshio
AU  - Hirano T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Antigens, CD)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Growth Inhibitors)
RN  - 0 (IL6ST protein, human)
RN  - 0 (Il6st protein, mouse)
RN  - 0 (Interleukin-6)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - 0 (Stat3 protein, mouse)
RN  - 0 (Trans-Activators)
RN  - 133483-10-0 (Cytokine Receptor gp130)
SB  - IM
MH  - Animals
MH  - Antigen Presentation/genetics
MH  - Antigens, CD/genetics/physiology
MH  - Bone Marrow Cells/cytology/immunology/metabolism
MH  - Cell Differentiation/genetics/*immunology
MH  - Cytokine Receptor gp130
MH  - DNA-Binding Proteins/*metabolism/physiology
MH  - Dendritic Cells/*cytology/*immunology/metabolism
MH  - Growth Inhibitors/deficiency/genetics/physiology
MH  - Humans
MH  - Interleukin-6/deficiency/genetics/*physiology
MH  - Lipopolysaccharides/antagonists & inhibitors/pharmacology
MH  - Membrane Glycoproteins/genetics/physiology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - STAT3 Transcription Factor
MH  - Signal Transduction/genetics/*immunology
MH  - Spleen/cytology/immunology
MH  - T-Lymphocytes/immunology/metabolism
MH  - Trans-Activators/*metabolism/physiology
EDAT- 2004/09/10 05:00
MHDA- 2004/10/20 09:00
CRDT- 2004/09/10 05:00
PHST- 2004/09/10 05:00 [pubmed]
PHST- 2004/10/20 09:00 [medline]
PHST- 2004/09/10 05:00 [entrez]
AID - 173/6/3844 [pii]
AID - 10.4049/jimmunol.173.6.3844 [doi]
PST - ppublish
SO  - J Immunol. 2004 Sep 15;173(6):3844-54. doi: 10.4049/jimmunol.173.6.3844.