IL-6, IL-17 and Stat3 are required for auto-inflammatory syndrome development in mouse.
IL-6, IL-17 and Stat3 are required for auto-inflammatory syndrome development in mouse.
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DOI：
10.1038/s41598-018-34173-5
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发表时间：
2018-10-25
影响因子：
4.6
通讯作者：
Miyamoto T
中科院分区：
文献类型：
--
作者：
Oike T;Kanagawa H;Sato Y;Kobayashi T;Nakatsukasa H;Miyamoto K;Nakamura S;Kaneko Y;Kobayashi S;Harato K;Yoshimura A;Iwakura Y;Takeuchi T;Matsumoto M;Nakamura M;Niki Y;Miyamoto T
自身炎性综合征是一种临床上与类风湿性关节炎不同的病症，其特征在于组织如主要关节、皮肤和内脏中的全身性炎症。自主性先天免疫激活被认为会促进这种炎症，但潜在的病理机制尚未阐明，治疗策略也尚未建立。在这里，我们新建立了一个小鼠模型，其中IL-1信号在成年小鼠（hIL-1 cTg）中被条件性激活，并观察到与自身炎症综合征患者相似的表型。hIL-1 cTg小鼠血清中IL-6和IL-17水平显著升高，关节中信号转导和转录激活因子3（Stat 3）被激活。当我们将hIL-1 cTg与IL-6或IL-17缺陷小鼠或Stat 3条件性敲除小鼠杂交时，在hIL-1 cTg小鼠中观察到的表型显著改善。因此，IL-6、IL-17和Stat 3都代表了该综合征的潜在治疗靶点。
Auto-inflammatory syndrome, a condition clinically distinct from rheumatoid arthritis, is characterized by systemic inflammation in tissues such as major joints, skin, and internal organs. Autonomous innate-immune activation is thought to promote this inflammation, but underlying pathological mechanisms have not been clarified nor are treatment strategies established. Here, we newly established a mouse model in which IL-1 signaling is conditionally activated in adult mice (hIL-1 cTg) and observed phenotypes similar to those seen in auto-inflammatory syndrome patients. In serum of hIL-1 cTg mice, IL-6 and IL-17 levels significantly increased, and signal transducer and activator of transcription 3 (Stat3) was activated in joints. When we crossed hIL-1 cTg with either IL-6- or IL-17-deficient mice or with Stat3 conditional knockout mice, phenotypes seen in hIL-1 cTg mice were significantly ameliorated. Thus, IL-6, IL-17 and Stat3 all represent potential therapeutic targets for this syndrome.
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影响因子：
8.1
作者：
Karasawa T;Takahashi M
通讯作者：
Takahashi M
影响因子：
64.5
作者：
Kastner DL;Aksentijevich I;Goldbach-Mansky R
通讯作者：
Goldbach-Mansky R
影响因子：
158.5
作者：
De Benedetti, Fabrizio;Brunner, Hermine I.;Martini, Alberto
通讯作者：
Martini, Alberto
影响因子：
5.5
作者：
Isomaki, Pia;Junttila, Ilkka;Silvennoinen, Olli
通讯作者：
Silvennoinen, Olli
DOI：
10.1056/nejmoa0807865
发表时间：
2009-06-04
期刊：
The New England journal of medicine
影响因子：
--
作者：
Aksentijevich I;Masters SL;Ferguson PJ;Dancey P;Frenkel J;van Royen-Kerkhoff A;Laxer R;Tedgård U;Cowen EW;Pham TH;Booty M;Estes JD;Sandler NG;Plass N;Stone DL;Turner ML;Hill S;Butman JA;Schneider R;Babyn P;El-Shanti HI;Pope E;Barron K;Bing X;Laurence A;Lee CC;Chapelle D;Clarke GI;Ohson K;Nicholson M;Gadina M;Yang B;Korman BD;Gregersen PK;van Hagen PM;Hak AE;Huizing M;Rahman P;Douek DC;Remmers EF;Kastner DL;Goldbach-Mansky R
通讯作者：
Goldbach-Mansky R