摘要
树枝状的房间(DC ) 在造血的房间的一张次要的人口,生产类型我干扰素(IFN ) 和另外的 cytokines 并且为天生的免疫是必要的。他们也是有势力抗原演讲者并且调整适应免疫。在 DC 子类型血浆之中似细胞的 DC (pDC ) 生产类型的最高的数量我 IFN。另外,象 IL-12 和 IL-10 那样的支持 inflammatory 和反煽动性的 cytokines 响应象发信号的受体(TLR ) 一样并且在病毒的感染之上的代价在 DC 被导致。在 IRF 家庭的蛋白质控制 DC 活动的许多方面。IRF-8 和 IRF-4 为 DC 开发是必要的。他们差别控制四个 DC 子集的开发。IRF-8-/- 老鼠大部分缺乏 pDC 和 CD8alpha+ DC,当 IRF-4-/- 老鼠缺乏 CD4+DC 时。IRF-8-/- , IRF4-/- ,两倍猛烈老鼠有仅仅很少 CD8a-CD4-DC 那缺乏 MHC II。IRF 蛋白质也控制类型我在 DC 的 IFN 正式就职。IRF-7,在 TLR 发信号之上激活不仅在 pDC,而且在常规 DC (cDC ) 为 IFN 正式就职被要求, non-DC 房间打字。IRF-3 贡献在成纤维细胞感应的 IFN,在在 DC 感应的 IFN 是非必需的。我们的最近的证据揭示那种类型我在 DC 感应的 IFN 非常依赖于 IRF-8,它在 DC 在 IFN 基因正式就职的反馈阶段行动。类型我在 pDC 感应的 IFN 被 MyD88 调停依赖发信号小径,并且不同于在另外的房间采用的小径,它主要依靠 TLR3 和 RIG-I 家庭蛋白质。另外的支持 inflammatory cytokines 以一种 IRF-5 依赖方式被生产。然而, IRF-5 没为 IFN 正式就职被要求,建议为类型的正式就职的分开的机制的存在我 IFN 和其它支持 inflammatory cytokines。激活的 DC 接着生产的 IFN 和另外的 cytokines 预付 DC 成熟并且改变 DC 的显型和功能。这些过程也是可能的被 IRF 家庭蛋白质管理。
Dendritic cells (DC), although a minor population in hematopoietic cells, produce type I interferons (IFN) and other cytokines and are essential for innate immunity. They are also potent antigen presenters and regulate adaptive immunity. Among DC subtypes plasmacytoid DC (pDC) produce the highest amounts of type I IFN. In addition, pro- and anti-inflammatory cytokines such as IL-12 and IL-10 are induced in DC in response to Toll like receptor (TLR) signaling and upon viral infection. Proteins in the IRF family control many aspects of DC activity. IRF-8 and IRF-4 are essential for DC development. They differentially control the development of four DC subsets. IRF-8^-/- mice are largely devoid of pDC and CD8α^+ DC, while IRF-4^-/- mice lack CD4^+ DC. IRF-8^-/-, IRF4^-/-, double knock-out mice have only few CD8α CD4^-DC that lack MHC Ⅱ. IRF proteins also control type Ⅰ IFN induction in DC. IRF-7, activated upon TLR signaling is required for IFN induction not only in pDC, but also in conventional DC (cDC) and non-DC cell types. IRF-3, although contributes to IFN induction in fibroblasts, is dispensable in IFN induction in DC. Our recent evidence reveals that type Ⅰ IFN induction in DC is critically dependent on IRF-8, which acts in the feedback phase of IFN gene induction in DC. Type Ⅰ IFN induction in pDC is mediated by MyD88 dependent signaling pathway, and differs from pathways employed in other cells, which mostly rely on TLR3 and RIG-Ⅰ family proteins. Other pro-inflammatory cytokines are produced in an IRF-5 dependent manner. However, IRF-5 is not required for IFN induction, suggesting the presence of separate mechanisms for induction of type Ⅰ IFN and other pro-inflammatory cytokines. IFN and other cytokines produced by activated DC in turn advance DC maturation and change the phenotype and function of DC. These processes are also likely to be governed by IRF family proteins.
关键词
IRF
蛋白质
干扰素
树状细胞
dendritic cells, IRF-3, 4, 5, 7, 8, type Ⅰ interferon induction, activate transcription, signaling pathway dependence