Linked Life Data

16551679

Source:http://linkedlifedata.com/resource/pubmed/id/16551679

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pubmed-article:16551679pubmed:abstractTextDendritic cells (DCs) play an important role in innate and adaptive immune responses. In addition to their phagocytic activity, DCs present foreign antigens to naïve 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.lld:pubmed
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pubmed-article:16551679pubmed:authorpubmed-author:MatikainenSam...lld:pubmed
pubmed-article:16551679pubmed:authorpubmed-author:JulkunenIlkka...lld:pubmed
pubmed-article:16551679pubmed:authorpubmed-author:LehtonenAnneAlld:pubmed
pubmed-article:16551679pubmed:authorpubmed-author:StrengellMari...lld:pubmed
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pubmed-article:16551679pubmed:pagination1279-85lld:pubmed
pubmed-article:16551679pubmed:dateRevised2011-11-17lld:pubmed
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pubmed-article:16551679pubmed:year2006lld:pubmed
pubmed-article:16551679pubmed:articleTitleIL-21 enhances SOCS gene expression and inhibits LPS-induced cytokine production in human monocyte-derived dendritic cells.lld:pubmed
pubmed-article:16551679pubmed:affiliationDepartment of Viral Diseases and Immunology, National Public Health Institute, Mannerheimintie 166, FIN-00300 Helsinki, Finland. mari.strengell@ktl.filld:pubmed
pubmed-article:16551679pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:16551679pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed