Drice restrains Diap2-mediated inflammatory signalling and intestinal inflammation.
Drice restrains Diap2-mediated inflammatory signalling and intestinal inflammation.
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Drice限制了DIAP2介导的炎症信号传导和肠炎。
DOI：
10.1038/s41418-021-00832-w
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发表时间：
2022-01
影响因子：
12.4
通讯作者：
Meinander A
中科院分区：
文献类型：
--
作者：
Kietz C;Mohan AK;Pollari V;Tuominen IE;Ribeiro PS;Meier P;Meinander A
果蝇IAP蛋白Diap 2是NF-κB信号传导和先天免疫应答的关键介质。Diap 2是发生在肠道和气管上皮细胞中的局部免疫激活和脂肪体细胞中的全身免疫应答所必需的。我们已经发现Diap 2的转基因表达导致NF-κB靶基因的自发诱导，诱导果蝇中肠的慢性炎症，但不在脂肪体中。Drice是一种已知与Diap 2相互作用并形成稳定复合物的果蝇效应器胱天蛋白酶。我们已经发现，这种复合物的形成诱导其随后的降解，从而调节Diap 2的量驱动NF-κB信号在肠道中。一致地，Drice活性的丧失导致Diap 2的积累和慢性肠道炎症。有趣的是，Drice不干扰病原体诱导的信号传导，这表明它可以保护居民微生物诱导的免疫反应。因此，在无菌条件下饲养的转基因Diap 2果蝇和Drice突变果蝇中未检测到炎症。因此，我们表明Drice通过抑制Diap 2，阻止了肠道中不必要的炎症信号。
The Drosophila IAP protein, Diap2, is a key mediator of NF-κB signalling and innate immune responses. Diap2 is required for both local immune activation, taking place in the epithelial cells of the gut and trachea, and for mounting systemic immune responses in the cells of the fat body. We have found that transgenic expression of Diap2 leads to a spontaneous induction of NF-κB target genes, inducing chronic inflammation in the Drosophila midgut, but not in the fat body. Drice is a Drosophila effector caspase known to interact and form a stable complex with Diap2. We have found that this complex formation induces its subsequent degradation, thereby regulating the amount of Diap2 driving NF-κB signalling in the intestine. Concordantly, loss of Drice activity leads to accumulation of Diap2 and to chronic intestinal inflammation. Interestingly, Drice does not interfere with pathogen-induced signalling, suggesting that it protects from immune responses induced by resident microbes. Accordingly, no inflammation was detected in transgenic Diap2 flies and Drice-mutant flies reared in axenic conditions. Hence, we show that Drice, by restraining Diap2, halts unwanted inflammatory signalling in the intestine.
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影响因子：
23.8
作者：
Douglas AE
通讯作者：
Douglas AE
影响因子：
8.8
作者：
Clark RI;Salazar A;Yamada R;Fitz-Gibbon S;Morselli M;Alcaraz J;Rana A;Rera M;Pellegrini M;Ja WW;Walker DW
通讯作者：
Walker DW
影响因子：
4.3
作者：
Apidianakis Y;Rahme LG
通讯作者：
Rahme LG
DOI：
10.1073/pnas.0404952102
发表时间：
2005-01-25
影响因子：
11.1
作者：
Choe, KM;Lee, H;Anderson, KV
通讯作者：
Anderson, KV
影响因子：
11.4
作者：
Ferrandon, D;Jung, AC;Hoffmann, JA
通讯作者：
Hoffmann, JA