Involvement of suppressors of cytokine signaling in toll-like receptor–mediated block of dendritic cell differentiation
| Autor: | Klaus Heeg, Andrea Baetz, Holger Bartz, Alexander H. Dalpke, Nicole M. Avalos |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
CD14
Cellular differentiation Immunology Lipopolysaccharide Receptors Bone Marrow Cells Suppressor of Cytokine Signaling Proteins Dendritic cell differentiation Biology Biochemistry Monocytes Antigens CD1 Mice Suppressor of Cytokine Signaling 1 Protein Animals Antigen-presenting cell Cells Cultured Mice Knockout Mice Inbred BALB C Toll-like receptor Innate immune system Toll-Like Receptors Granulocyte-Macrophage Colony-Stimulating Factor Cell Differentiation Dendritic Cells Cell Biology Hematology Dendritic cell Immunity Innate Cell biology Signal transduction Signal Transduction |
| Zdroj: | Blood. 108:4102-4108 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2006-03-008946 |
| Popis: | Dendritic cells (DCs) are important sentinels within innate immunity, monitoring the presence of infectious microorganisms. They operate in 2 different maturation stages, with transition from immature to mature DCs being induced by activation of toll-like receptors (TLRs). However, TLRs are also expressed on precursor cells of DCs. Here we analyzed the effects of TLR stimulation during the process of granulocyte-macrophage–colony-stimulating factor (GM-CSF)–mediated in vitro generation of immature DCs from precursor cells. We show that TLR triggering deviated phenotypic and functional differentiation from CD14+ monocytes to CD1a+ DCs. Similar results were obtained when differentiation of murine myeloid DCs from bone marrow cells was analyzed. The inhibitory effects were independent of soluble factors. TLR stimulation in DC precursor cells induced proteins of the suppressor of cytokine signaling family (SOCS), which correlated with loss of sensitivity to GM-CSF. Overexpression of SOCS-1 abolished GM-CSF signal transduction. Moreover, forced SOCS-1 expression in DC precursors mimicked the inhibitory effects on DC generation observed for TLR stimulation. The results indicate that TLR stimulation during the period of DC generation interferes with and deviates DC differentiation and that these effects are mediated particularly by SOCS-1. |
| Databáze: | OpenAIRE |
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