Aryl hydrocarbon receptor control of a disease tolerance defence pathway.
Aryl hydrocarbon receptor control of a disease tolerance defence pathway.
复制标题
DOI：
10.1038/nature13323
复制
发表时间：
2014-07-10
期刊：
影响因子：
64.8
通讯作者：
Puccetti P
中科院分区：
文献类型：
--
作者：
Bessede A;Gargaro M;Pallotta MT;Matino D;Servillo G;Brunacci C;Bicciato S;Mazza EM;Macchiarulo A;Vacca C;Iannitti R;Tissi L;Volpi C;Belladonna ML;Orabona C;Bianchi R;Lanz TV;Platten M;Della Fazia MA;Piobbico D;Zelante T;Funakoshi H;Nakamura T;Gilot D;Denison MS;Guillemin GJ;DuHadaway JB;Prendergast GC;Metz R;Geffard M;Boon L;Pirro M;Iorio A;Veyret B;Romani L;Grohmann U;Fallarino F;Puccetti P
疾病耐受性是指宿主减少感染对宿主健康的影响的能力。对疾病耐受途径的分析可以为治疗感染和其他炎症性疾病提供新的方法。通常，最初暴露在细菌脂多糖(LPS)下会导致对进一步的LPS挑战(内毒素耐受)的不稳定状态。我们发现，首次暴露于脂多糖可激活配体操纵的转录因子芳香烃受体(AhR)和肝酶色氨酸2，3-双加氧酶2，为前者提供激活配体，从而下调早期炎症基因的表达。然而，在内毒素再激发时，AhR仅在吲哚胺2，3-双加氧酶1(IDO1)存在的情况下参与全身炎症的长期调节。AHR复合体相关的Src激酶活性促进IDO1的磷酸化和信号转导能力。由此产生的内毒素耐受状态被发现在革兰氏阴性和革兰氏阳性感染中保护小鼠免受免疫病理学的影响，这表明AhR在促进宿主健康方面发挥了作用。
Disease tolerance is the ability of the host to reduce the impact of infection on host fitness. Analysis of disease tolerance pathways could provide new approaches for treating infections and other inflammatory diseases. Typically, an initial exposure to bacterial lipopolysaccharide (LPS) induces a state of refractoriness to further LPS challenge (“endotoxin tolerance”). We found that a first exposure to LPS activated the ligand-operated transcription factor aryl hydrocarbon receptor (AhR) and the hepatic enzyme tryptophan 2,3-dioxygenase 2, which provided an activating ligand to the former, to downregulate early inflammatory gene expression. However, on LPS rechallenge, AhR engaged in long-term regulation of systemic inflammation only in the presence of indoleamine 2,3-dioxygenase 1 (IDO1). AhR complex-associated Src kinase activity promoted IDO1 phosphorylation and signaling ability. The resulting endotoxin-tolerant state was found to protect mice against immunopathology in gram-negative and gram-positive infections, pointing to a role for AhR in contributing to host fitness.
登录
查看更多内容
影响因子：
4.4
作者：
Jung, In Duk;Lee, Min-Goo;Park, Yeong-Min
通讯作者：
Park, Yeong-Min
影响因子：
30.5
作者：
Fallarino, F;Grohmann, U;Puccetti, P
通讯作者：
Puccetti, P
影响因子：
30.5
作者：
Grohmann, U;Orabona, C;Puccetti, P
通讯作者：
Puccetti, P
通过芳基烃受体介导的蛋白酪氨酸激酶C-SRC激活的FRET分析。
影响因子：
3
作者：
Dong, Bin;Cheng, Wei;Li, Wen;Zheng, Jie;Wu, Dalei;Matsumura, Fumio;Vogel, Christoph Franz Adam
通讯作者：
Vogel, Christoph Franz Adam
DOI：
10.1084/jem.20090560
发表时间：
2009-08-31
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kimura A;Naka T;Nakahama T;Chinen I;Masuda K;Nohara K;Fujii-Kuriyama Y;Kishimoto T
通讯作者：
Kishimoto T