PMID- 21844389
OWN - NLM
STAT- MEDLINE
DCOM- 20111109
LR  - 20110908
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 187
IP  - 6
DP  - 2011 Sep 15
TI  - Suppressor of cytokine signaling 2 is a feedback inhibitor of TLR-induced 
      activation in human monocyte-derived dendritic cells.
PG  - 2875-84
LID - 10.4049/jimmunol.1003348 [doi]
AB  - Dendritic cells (DCs) are key players in initiating and directing the immune 
      response. Therefore, their activation state and functional differentiation need 
      to be tightly controlled. The activating stimuli and their signaling networks 
      have long been an area of focus in DC research. Recent investigations have also 
      shed light on the mechanisms of counterregulation and fine-tuning of DC 
      functions. One class of proteins involved in these processes is the family of 
      suppressors of cytokine signaling (SOCS), whose members were originally described 
      as feedback inhibitors of cytokine-induced JAK/STAT signaling. Essential roles in 
      DC function have been assigned to SOCS1 and SOCS3. In this article, we show that 
      SOCS2 also is involved in DC regulation. In human and in murine DCs, SOCS2 is a 
      highly TLR-responsive gene, which is expressed in a time-delayed fashion 
      beginning 8 h after TLR ligation. Functionally, silencing of SOCS2 in DCs results 
      in hyperphosphorylation of STAT3 at later time points. As a consequence, 
      SOCS2-deficient DCs secrete increased amounts of the cytokines IL-1beta and IL-10, 
      both being transcriptional targets of STAT3. We propose a model in which SOCS2 
      acts as a negative regulator of TLR-induced DC activation. The delayed expression 
      of SOCS2 provides a mechanism of late-phase counterregulation and limitation of 
      inflammation-driving DC activity.
FAU - Posselt, Gernot
AU  - Posselt G
AD  - Division of Allergy and Immunology, Department of Molecular Biology, Paris Lodron 
      University of Salzburg, 5020 Salzburg, Austria.
FAU - Schwarz, Harald
AU  - Schwarz H
FAU - Duschl, Albert
AU  - Duschl A
FAU - Horejs-Hoeck, Jutta
AU  - Horejs-Hoeck J
LA  - eng
PT  - Journal Article
DEP - 20110815
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (RNA, Small Interfering)
RN  - 0 (SOCS2 protein, human)
RN  - 0 (Suppressor of Cytokine Signaling Proteins)
RN  - 0 (Toll-Like Receptors)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cell Differentiation/*immunology
MH  - Cell Separation
MH  - Dendritic Cells/cytology/*immunology/metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Feedback, Physiological
MH  - Flow Cytometry
MH  - Humans
MH  - Lymphocyte Culture Test, Mixed
MH  - Mice
MH  - Monocytes/cytology/immunology/metabolism
MH  - RNA, Small Interfering
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction/*immunology
MH  - Suppressor of Cytokine Signaling Proteins/*immunology/metabolism
MH  - Toll-Like Receptors/immunology/metabolism
EDAT- 2011/08/17 06:00
MHDA- 2011/11/10 06:00
CRDT- 2011/08/17 06:00
PHST- 2011/08/17 06:00 [entrez]
PHST- 2011/08/17 06:00 [pubmed]
PHST- 2011/11/10 06:00 [medline]
AID - jimmunol.1003348 [pii]
AID - 10.4049/jimmunol.1003348 [doi]
PST - ppublish
SO  - J Immunol. 2011 Sep 15;187(6):2875-84. doi: 10.4049/jimmunol.1003348. Epub 2011 
      Aug 15.