PMID- 16849477
OWN - NLM
STAT- MEDLINE
DCOM- 20060906
LR  - 20190516
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 177
IP  - 3
DP  - 2006 Aug 1
TI  - Dendritic cells transduced with SOCS-3 exhibit a tolerogenic/DC2 phenotype that 
      directs type 2 Th cell differentiation in vitro and in vivo.
PG  - 1679-88
AB  - Dendritic cells (DCs) have been suggested to direct a type of Th differentiation 
      through their cytokine profile, e.g., high IL-12/IL-23 for Th1 (named 
      DC1/immunogenic DCs) and IL-10 for Th2 (DC2/tolerogenic DCs). Suppressor of 
      cytokine signaling (SOCS)-3 is a potent inhibitor of Stat3 and Stat4 transduction 
      pathways for IL-23 and IL-12, respectively. We thus hypothesize that an enhanced 
      SOCS-3 expression in DCs may block the autocrine response of IL-12/IL-23 in these 
      cells, causing them to become a DC2-type phenotype that will subsequently promote 
      Th2 polarization of naive T cells. Indeed, in the present study we found that 
      bone marrow-derived DCs transduced with SOCS-3 significantly inhibited 
      IL-12-induced activation of Stat4 and IL-23-induced activation of Stat3. These 
      SOCS-3-transduced DCs expressed a low level of MHC class II and CD86 on their 
      surface, produced a high level of IL-10 but low levels of IL-12 and IFN-gamma, 
      and expressed a low level of IL-23 p19 mRNA. Functionally, SOCS-3-transduced DCs 
      drove naive myelin oligodendrocyte glycoprotein-specific T cells to a strong Th2 
      differentiation in vitro and in vivo. Injection of SOCS-3-transduced DCs 
      significantly suppressed experimental autoimmune encephalomyelitis, a Th1 
      cell-mediated autoimmune disorder of the CNS and an animal model of multiple 
      sclerosis. These results indicate that transduction of SOCS-3 in DCs is an 
      effective approach to generating tolerogenic/DC2 cells that then skew immune 
      response toward Th2, thus possessing therapeutic potential in Th1-dominant 
      autoimmune disorders such as multiple sclerosis.
FAU - Li, Yonghai
AU  - Li Y
AD  - Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, 
      USA.
FAU - Chu, Niansheng
AU  - Chu N
FAU - Rostami, Abdolmohamad
AU  - Rostami A
FAU - Zhang, Guang-Xian
AU  - Zhang GX
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
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 (Il23a protein, mouse)
RN  - 0 (Interleukin-23)
RN  - 0 (Interleukin-23 Subunit p19)
RN  - 0 (Interleukins)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT4 Transcription Factor)
RN  - 0 (Socs3 protein, mouse)
RN  - 0 (Stat3 protein, mouse)
RN  - 0 (Stat4 protein, mouse)
RN  - 0 (Suppressor of Cytokine Signaling 3 Protein)
RN  - 0 (Suppressor of Cytokine Signaling Proteins)
RN  - 187348-17-0 (Interleukin-12)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cell Differentiation/genetics/*immunology
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Dendritic Cells/*immunology/*metabolism/transplantation
MH  - Encephalomyelitis, Autoimmune, Experimental/genetics/immunology/prevention & 
      control
MH  - Female
MH  - Gene Expression Regulation/immunology
MH  - Immune Tolerance/*genetics
MH  - *Immunophenotyping
MH  - Interleukin-12/antagonists & inhibitors/physiology
MH  - Interleukin-23
MH  - Interleukin-23 Subunit p19
MH  - Interleukins/antagonists & inhibitors/physiology
MH  - Lipopolysaccharides/pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Molecular Sequence Data
MH  - STAT3 Transcription Factor/antagonists & inhibitors/metabolism
MH  - STAT4 Transcription Factor/antagonists & inhibitors/metabolism
MH  - Signal Transduction/genetics/immunology
MH  - Suppressor of Cytokine Signaling 3 Protein
MH  - Suppressor of Cytokine Signaling Proteins/biosynthesis/*genetics/physiology
MH  - Th2 Cells/cytology/*immunology
MH  - *Transduction, Genetic
EDAT- 2006/07/20 09:00
MHDA- 2006/09/07 09:00
CRDT- 2006/07/20 09:00
PHST- 2006/07/20 09:00 [pubmed]
PHST- 2006/09/07 09:00 [medline]
PHST- 2006/07/20 09:00 [entrez]
AID - 177/3/1679 [pii]
AID - 10.4049/jimmunol.177.3.1679 [doi]
PST - ppublish
SO  - J Immunol. 2006 Aug 1;177(3):1679-88. doi: 10.4049/jimmunol.177.3.1679.