ISG15: leading a double life as a secreted molecule.
ISG15: leading a double life as a secreted molecule.
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ISG15：作为分泌分子的双重寿命。
DOI：
10.1038/emm.2013.36
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发表时间：
2013-04-12
影响因子：
12.8
通讯作者：
Casanova, Jean-Laurent
中科院分区：
文献类型：
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作者：
Bogunovic, Dusan;Boisson-Dupuis, Stephanie;Casanova, Jean-Laurent
ISG15是一种众所周知的细胞内泛素样分子，参与isg酰化。然而，最近的一项研究重新提出了20年前首次提出的概念，即ISG15也是一种分泌分子。人中性粒细胞、单核细胞和淋巴细胞可以释放ISG15，尽管这种蛋白没有可检测到的信号肽序列。在粒细胞的分泌颗粒中也发现了ISG15。ISG15分泌的机制尚不清楚。分泌的ISG15至少作用于T淋巴细胞和自然杀伤（NK）淋巴细胞，诱导干扰素(IFN)-γ的产生。然而，ISG15刺激这些细胞的机制仍不清楚。ISG15和IFN-γ似乎定义了一种先天回路，该回路在粒细胞和NK细胞之间优先起作用，但并非完全起作用。在小鼠和人类中，遗传性ISG15缺乏症与严重的分枝杆菌疾病有关。这种传染性表型可能是由于缺乏分泌ISG15，因为患有其他先天性IFN-γ免疫错误的患者和小鼠也表现出分枝杆菌疾病。除了提出机制问题外，本文描述的研究还为各个方面的临床研究铺平了道路，从在感染性疾病患者中使用重组ISG15到在炎症性疾病患者中使用ISG15阻断剂。
ISG15 is a well-known intracellular ubiquitin-like molecule involved in ISGylation. However, a recent study has revived the notion first put forward two decades ago that ISG15 is also a secreted molecule. Human neutrophils, monocytes and lymphocytes can release ISG15, even though this protein has no detectable signal peptide sequence. ISG15 has also been found in the secretory granules of granulocytes. The mechanism underlying ISG15 secretion is unknown. Secreted ISG15 acts on at least T and natural killer (NK) lymphocytes, in which it induces interferon (IFN)-γ production. However, the mechanism by which ISG15 stimulates these cells also remains unclear. ISG15 and IFN-γ seem to define an innate circuit that operates preferentially, but not exclusively, between granulocytes and NK cells. Inherited ISG15 deficiency is associated with severe mycobacterial disease in both mice and humans. This infectious phenotype probably results from the lack of secreted ISG15, because patients and mice with other inborn errors of IFN-γ immunity also display mycobacterial diseases. In addition to raising mechanistic issues, the studies described here pave the way for clinical studies of various aspects, ranging from the use of recombinant ISG15 in patients with infectious diseases to the use of ISG15-blocking agents in patients with inflammatory diseases.
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DOI：
10.1126/science.1224026
发表时间：
2012-09-28
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
Bogunovic D;Byun M;Durfee LA;Abhyankar A;Sanal O;Mansouri D;Salem S;Radovanovic I;Grant AV;Adimi P;Mansouri N;Okada S;Bryant VL;Kong XF;Kreins A;Velez MM;Boisson B;Khalilzadeh S;Ozcelik U;Darazam IA;Schoggins JW;Rice CM;Al-Muhsen S;Behr M;Vogt G;Puel A;Bustamante J;Gros P;Huibregtse JM;Abel L;Boisson-Dupuis S;Casanova JL
通讯作者：
Casanova JL
影响因子：
3.7
作者：
Boisson-Dupuis, Stephanie;El Baghdadi, Jamila;Casanova, Jean-Laurent
通讯作者：
Casanova, Jean-Laurent
X连锁对分枝杆菌的敏感性是由NEMO中的突变损害CD40依赖性IL-12产生引起的。
影响因子：
15.3
作者：
Filipe-Santos, Orchidee;Bustamante, Jacinta;Haverkamp, Margje H;Vinolo, Emilie;Ku, Cheng-Lung;Puel, Anne;Frucht, David M;Christel, Karin;von Bernuth, Horst;Jouanguy, Emmanuelle;Feinberg, Jacqueline;Durandy, Anne;Senechal, Brigitte;Chapgier, Ariane;Vogt, Guillaume;de Beaucoudrey, Ludovic;Fieschi, Claire;Picard, Capucine;Garfa, Meriem;Chemli, Jalel;Bejaoui, Mohamed;Tsolia, Maria N;Kutukculer, Necil;Plebani, Alessandro;Notarangelo, Luigi;Bodemer, Christine;Geissmann, Frederic;Israel, Alain;Veron, Michel;Knackstedt, Maike;Barbouche, Ridha;Abel, Laurent;Magdorf, Klaus;Gendrel, Dominique;Agou, Fabrice;Holland, Steven M;Casanova, Jean-Laurent
通讯作者：
Casanova, Jean-Laurent
影响因子：
32.4
作者：
Pérez de Diego R;Sancho-Shimizu V;Lorenzo L;Puel A;Plancoulaine S;Picard C;Herman M;Cardon A;Durandy A;Bustamante J;Vallabhapurapu S;Bravo J;Warnatz K;Chaix Y;Cascarrigny F;Lebon P;Rozenberg F;Karin M;Tardieu M;Al-Muhsen S;Jouanguy E;Zhang SY;Abel L;Casanova JL
通讯作者：
Casanova JL
影响因子：
30.5
作者：
通讯作者：
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