细胞因子与受体课件.ppt

* Figure?1. Interferon (IFN) is produced by the plasmacytoid dendritic cell (pDC). Accumulation of RNA-DNA hybrids may be recognized by TLRs in endosomes or by the RNA helicases RIG-1 and Mda-5 in the cytoplasm. The recognition leads to a cascade of signal transduction events, resulting in the phosphorylation of transcription factors (interferon regulatory factors (IRFs)) and the induction of the type I interferon genes. Secreted interferon is recognized by interferon receptors (IFNARs) I and II and induces a cascade leading to the induction of interferon-inducible genes. Many of the interferon-inducible genes are cytokines, chemokines and apoptosis-related genes.Kim Caesar 浆细胞样树突状细胞(pDC) 常染色体隐性遗传性脑病收购小头畸形，脑钙化的特点 The interferon response Viral infection and replication introduces single- stranded RNA (ssRNA), double-stranded RNA (dsRNA) and DNA:RNA hybrid byproducts. In response to these challenges, interferon is produced by a particular cell type, the plasmacytoid dendritic cell (pDC), which carries both interferon receptors and the pattern-recognizing toll-like receptors (TLRs). TLRs recognize dsRNA, ssRNA or CpG oligonucleotides. Several investigations have shown that ssRNA and dsRNA as well as other complexes of nucleic acids, including those containing lupus autoantigens such as U1snRNA11,12, stimulate the activation of pDCs and the production of interferon alpha (Fig. 1). This activation occurs via TLR7. On the other hand, dsRNA can be recognized by TLR3 in endosomes or by the RNA helicases RIG-1 and Mda-5 in the cytoplasm. This recognition leads to a cascade of signal transduction events and to the formation of complexes of phosphorylated proteins, depending on the activated pathway, leading ultimately to the phosphorylation of transcription factors (interferon regulatory factors 3, 5, 7 and 9) and the induction of the type I interferon genes. In turn, secreted interferon is recognized by interferon receptors I and II, and a cascade via STAT1 and STAT2 lea