PMID- 16551679
OWN - NLM
STAT- MEDLINE
DCOM- 20060810
LR  - 20231213
IS  - 0741-5400 (Print)
IS  - 0741-5400 (Linking)
VI  - 79
IP  - 6
DP  - 2006 Jun
TI  - IL-21 enhances SOCS gene expression and inhibits LPS-induced cytokine production 
      in human monocyte-derived dendritic cells.
PG  - 1279-85
AB  - Dendritic cells (DCs) play an important role in innate and adaptive immune 
      responses. In addition to their phagocytic activity, DCs present foreign antigens 
      to naive T cells and regulate the development of adaptive immune responses. Upon 
      contact with DCs, activated T cells produce large quantities of cytokines such as 
      interferon-gamma (IFN-gamma) and interleukin (IL)-21, which have important 
      immunoregulatory functions. Here, we have analyzed the effect of IL-21 and 
      IFN-gamma on lipopolysaccharide (LPS)-induced maturation and cytokine production 
      of human monocyte-derived DCs. IL-21 and IFN-gamma receptor genes were expressed 
      in high levels in immature DCs. Pretreatment of immature DCs with IL-21 inhibited 
      LPS-stimulated DC maturation and expression of CD86 and human leukocyte antigen 
      class II (HLAII). IL-21 pretreatment also dramatically reduced LPS-stimulated 
      production of tumor necrosis factor alpha, IL-12, CC chemokine ligand 5 (CCL5), 
      and CXC chemokine ligand 10 (CXCL10) but not that of CXCL8. In contrast, 
      IFN-gamma had a positive feedback effect on immature DCs, and it enhanced 
      LPS-induced DC maturation and the production of cytokines. IL-21 weakly induced 
      the expression Toll-like receptor 4 (TLR4) and translation initiation region 
      (TIR) domain-containing adaptor protein (TIRAP) genes, whereas the expression of 
      TIR domain-containing adaptor-inducing IFN-beta (TRIF), myeloid differentiation 
      (MyD88) 88 factor, or TRIF-related adaptor molecule (TRAM) genes remained 
      unchanged. However, IL-21 strongly stimulated the expression of suppressor of 
      cytokine signaling (SOCS)-1 and SOCS-3 genes. SOCS are known to suppress DC 
      functions and interfere with TLR4 signaling. Our results demonstrate that IL-21, 
      a cytokine produced by activated T cells, can directly inhibit the activation and 
      cytokine production of myeloid DCs, providing a negative feedback loop between 
      DCs and T lymphocytes.
FAU - Strengell, Mari
AU  - Strengell M
AD  - Department of Viral Diseases and Immunology, National Public Health Institute, 
      Mannerheimintie 166, FIN-00300 Helsinki, Finland. mari.strengell@ktl.fi
FAU - Lehtonen, Anne
AU  - Lehtonen A
FAU - Matikainen, Sampsa
AU  - Matikainen S
FAU - Julkunen, Ilkka
AU  - Julkunen I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060321
PL  - England
TA  - J Leukoc Biol
JT  - Journal of leukocyte biology
JID - 8405628
RN  - 0 (CCL5 protein, human)
RN  - 0 (Chemokine CCL5)
RN  - 0 (Chemokines, CC)
RN  - 0 (Chemokines, CXC)
RN  - 0 (Cytokines)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (IL21R protein, human)
RN  - 0 (Interleukin-21 Receptor alpha Subunit)
RN  - 0 (Interleukins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Interferon)
RN  - 0 (Receptors, Interleukin)
RN  - 0 (Receptors, Interleukin-1)
RN  - 0 (Receptors, Interleukin-21)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (SOCS1 protein, human)
RN  - 0 (SOCS3 protein, human)
RN  - 0 (Suppressor of Cytokine Signaling 1 Protein)
RN  - 0 (Suppressor of Cytokine Signaling 3 Protein)
RN  - 0 (Suppressor of Cytokine Signaling Proteins)
RN  - 0 (TIRAP protein, human)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 187348-17-0 (Interleukin-12)
RN  - 82115-62-6 (Interferon-gamma)
RN  - MKM3CA6LT1 (interleukin-21)
SB  - IM
MH  - Cell Communication
MH  - Cells, Cultured/drug effects/immunology/metabolism
MH  - Chemokine CCL5
MH  - Chemokines, CC/biosynthesis/genetics
MH  - Chemokines, CXC/biosynthesis/genetics
MH  - Cytokines/*biosynthesis/genetics
MH  - Dendritic Cells/*drug effects/immunology/metabolism
MH  - Feedback, Physiological
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation/*drug effects
MH  - HLA-DR Antigens/biosynthesis
MH  - Humans
MH  - Interferon-gamma/pharmacology
MH  - Interleukin-12/biosynthesis/genetics
MH  - Interleukin-21 Receptor alpha Subunit
MH  - Interleukins/*pharmacology/physiology
MH  - Intracellular Signaling Peptides and Proteins/genetics
MH  - Lipopolysaccharides/antagonists & inhibitors
MH  - Lymphocyte Activation
MH  - Macrophages/drug effects/metabolism
MH  - Membrane Glycoproteins/biosynthesis/genetics
MH  - RNA, Messenger/biosynthesis/genetics
MH  - Receptors, Interferon/biosynthesis/genetics
MH  - Receptors, Interleukin/biosynthesis/genetics
MH  - Receptors, Interleukin-1/biosynthesis/genetics
MH  - Receptors, Interleukin-21
MH  - Recombinant Proteins/pharmacology
MH  - Repressor Proteins/*biosynthesis/genetics
MH  - Suppressor of Cytokine Signaling 1 Protein
MH  - Suppressor of Cytokine Signaling 3 Protein
MH  - Suppressor of Cytokine Signaling Proteins/*biosynthesis/genetics
MH  - T-Lymphocytes/immunology/*metabolism
MH  - Toll-Like Receptor 4/biosynthesis/genetics
MH  - Tumor Necrosis Factor-alpha/biosynthesis/genetics
MH  - Interferon gamma Receptor
EDAT- 2006/03/23 09:00
MHDA- 2006/08/11 09:00
CRDT- 2006/03/23 09:00
PHST- 2006/03/23 09:00 [pubmed]
PHST- 2006/08/11 09:00 [medline]
PHST- 2006/03/23 09:00 [entrez]
AID - jlb.0905503 [pii]
AID - 10.1189/jlb.0905503 [doi]
PST - ppublish
SO  - J Leukoc Biol. 2006 Jun;79(6):1279-85. doi: 10.1189/jlb.0905503. Epub 2006 Mar 
      21.