Identification of specific regulatory elements in the IL-10 locus. Dependence of IL-10 as well as IL-12 production on signalling adaptor molecules
comment: Our lab has obtained data on the dependence of IL-10 as well as IL-12 production on signalling adaptor molecules. Dendritic cells (DC) arise in the bone marrow and circulate through blood or tissue; upon pathogen challenge DC subsequently migrate to lymphoid organs to initiate immune responses (Banchereau et al., 1998). DC act as sentinels for pathogens forming the interface between the innate and adaptive immune response. In addition they are flexible in driving both Th1 and Th2 responses (Boonstra, Rajsbaum et al., 2003). Mouse DC can be derived from bone marrow (BM), which, after culture results in myeloid DC and plasmacytoid precursor DC (pDC), or can be directly isolated from the spleen, lymph nodes or tissue as classical DC (CD11cbright, CD8+ or CD8-) or plasmacytoid pDC. We have shown that macrophages, myeloid DC and plasmacytoid DC have the intrinsic capacity to produce different amounts of IL-12 upon stimulation through TLR9 and TLR4. Some of this, but not all is accounted for by endogenous IL-10 production which inhibits the subsequent production of IL-12. In this respect we have identified specific regulatory elements in the IL-10 locus which are present in DC and macrophages but not T cells (Saraiva et al., 2005). We have now shown that both IL-10 as well as IL-12 production is dependent on the signalling adaptor molecules either MyD88 or TRIF, respectively in response to CpG, LPS or PolyIC. This work has been published in the J.Immunology (Boonstra, Rajsbaum et al, 2006).
type: data set
type: proteomics dataset
has document: Identification of a macrophage-specific chromatin signature in the IL-10 locus.
has document: Dendritic cells and the control of immunity.
has document: Macrophages and myeloid DC, but not plasmacytoid DC, produce IL-10 in response to MyD88- and TRIF- dependent TLR signals, and TLR-independent signals.
has organism type: Mus musculus
has cell type: dendritic cell
has cell type: T cell
has cell type: macrophage
has molecule type: Interleukin-10
has molecule type: Interleukin-12 cytokine
has molecule type: Myeloid differentiation primary response (88)
has molecule type: TIR-domain-containing adapter-inducing interferon beta
has stimulus type: CpG
has stimulus type: lipopolysaccharide
has stimulus type: Polyinosinic acid:polycytidylic acid
related to instance: Mechanisms for DC-induced Th1 development and the molecular pathways for inducing Th1 cells producing IFN-gamma / IL 10
has knowledgeable: Anne O'Garra