S1PR1-mediated IFNAR1 degradation modulates plasmacytoid dendritic cell interferon-α autoamplification
由S1PR1介导的IFNAR1降解可以调节浆细胞样树突状细胞
α-干扰素的自动扩增／信号放大
ma是什么意思摘要：
Blunting immunopathology without abolishing host defen is the foundation for safe and effective modulation of infectious and autoimmune dias.
没有废除宿主防御机制的免疫病理钝化是安全、有效调节传染病和自身免疫性疾病的基础。
Sphingosine 1-phosphate receptor 1 (S1PR1) agonists are effective in treating infectious and multiple autoimmune pathologies; however, mechanisms underlying their clinical efficacy are yet to be fully elucidated.
1-磷酸-鞘氨醇受体1（S1PR1）促效药对于治疗传染病和多种自身免疫性疾病是有效的，然
而，其临床疗效的具体机制尚未被完全阐明。
Here, we uncover an unexpected mechanism of convergence between S1PR1 and interferon alpha receptor 1 (IFNAR1) signaling pathways.
在本研究中，我们意外发现S1PR1与α-干扰素受体1（IFNAR1）信号通路之间的趋同／聚集机制。
Activation of S1PR1 signaling by pharmacological tools or endogenous ligand sphingosine-1 phosphate (S1P) inhibits type 1 IFN respons that exacerbate numerous pathogenic conditions.
通过药理作用或内源性配体1-磷酸-鞘氨醇（S1P）发出信号激活S1PR1可以抑制1型干扰素应答，这将提供大量致病条件。
Mechanistically, S1PR1 lectively suppress the type I IFN autoamplification loop in plasmacytoid dendritic cells (pDCs), a specialized DC subt, for robust type I IFN relea.
机械地说，S1PR1能够选择性抑制1型干扰素在浆细胞样树突状细胞（pDCs，一种特殊的树突状细胞亚群，可以释放大量1型干扰素）内的自身扩增循环。
S1PR1 agonist suppression is pertussis toxin-resistant, but inhibited by an S1PR1 C-terminal–derived transactivating transcriptional activator (Tat)-fusion peptide that blocks receptor internalization.
抗百日咳毒素可以抑制S1PR1促效药，但是是通过一个来自S1PR1 C末端的反式激活转录活化因子Tat-融合肽（可以封闭受体内化作用）来发挥抑制作用的。
S1PR1 agonist treatment accelerates turnover of IFNAR1, suppress signal transducer and activator of transcription 1 (STAT1) phosphorylation, and down-modulates total STAT1 levels, thereby inactivating the autoamplification loop.
S1PR1促效药的治疗机制是加速IFNAR1的循环，抑制转录信号转导器和活化剂1（STAT1）的磷酸化作用，以及下调总的STAT1水平，从而达到抑制自身扩增循环的效果。
高一英语周报答案
Inhibition of S1P-S1PR1 signaling in vivo using the lective antagonist Ex26 significantly elevates IFN-α production in respon to CpG-A.
使用选择性拮抗剂Ex26来抑制体内的S1P-S1PR1信号可以显著提升在应答CpG-A时α-干扰素的产量。英语 mp3
Thus, multiple lines of evidence demonstrate that S1PR1 signaling ts the nsitivity of pDC amplification of IFN respons, thereby blunting pathogenic immune respons.
因此，大量证据表明S1PR1信号可以调节pDC放大干扰素应答的敏感性，从而钝化致病性免疫应答。
The data illustrate a lipid G-protein coupled receptor (GPCR)-IFNAR1 regulatory loop that balances effective and detrimental immune respons and elevated en- dogenous S1PR1 signaling.
这些数据表明一个脂质G蛋白偶联受体（GPCR）-IFNAR1调控循环能够平衡有效的和有害的免疫应答以及增加的内源性S1PR1信号。
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This mechanism will likely be advantageous in individuals subject to a range of inflammatory conditions.
这种机制可能会导致个体陷入一系列炎症状态中。a lot of
关键词：
sphingosine 1-phosphate | S1PR1 | plasmacytoid dendritic cell | interferon-α | IFNAR1
1-磷酸-鞘氨醇；1-磷酸-鞘氨醇受体1；浆细胞样树突状细胞；α-干扰素；α-干扰素受体1parately
前言：
Plasmacytoid dendritic cells (pDCs) are a rare innate immune cell population in mice known for their ability to produce large quantities of type 1 IFN (IFN-I) following stimulation with viral or cellular nucleic acids.
小鼠体内的pCDs是一种罕见的天然免疫细胞群，在病毒或细胞内核酸的刺激它能够产生大量IFN-1。laziofly
strict是什么意思
Moreover, IFN-α signaling promotes autoimmune (1), viral (2–5), and bacterial dia pathogenesis (6).
此外，IFN-α信号可以促进自身免疫、病毒性和细菌性疾病的发病机理。
Suppression of IFN-α signaling has demonstrated efficacy in multiple autoimmune mou models (7–9) and during influenza viral infection (4, 10); however, the mechanism by which sphingosine 1-phosphate receptor 1 (S1PR1) signaling prevents IFN-α amplification during the dia states is currently unknown.
IFN-α的抑制作用已经在多种自身免疫小鼠模型的疗效和在流感病毒感染期间被阐明，然而在这些发病状态中S1PR1信号阻止IFN-α自动扩增的机制尚不清楚。
Recently, we found direct evidence that IFN-I induction and the concomitant cytokine storm were chemically tractable using sphingosine 1-phosphate receptor 1 (S1PR1) lective agonists.
最近，我们发现了使用S1PR1选择性促效药可以诱导IFN-I并且伴随着的细胞因子增加的直
pepco接证据。
S1PR1 agonist therapy suppresd innate immune cell recruitment and cytokine-chemokine production and improved survival without postponing viral clearance, indicating that cytokine storm was causative of dia pathogenesis and that S1P agonist therapy could suppress detrimental innate immune respons without hindering virus control (10, 11).
英语作文格式S1PR1促效药疗法可以抑制天然免疫细胞的补充和细胞因子、趋化因子的产生，可以在没有延迟清除病毒的情况下提高存活率，这表明细胞因子的增加是疾病发病机理的原因，也表明在没有妨碍控制病毒的情况下S1P促效药疗法能够抑制有害的天然免疫应答。
The identification that S1PR1 agonists suppress detrimental innate immune respons indicates that S1PR1 probes may rve as viable drug leads to curb resulting immune pathology during both infectious and autoimmune dia states.
