Inflammasome-mediated disease animal models reveal roles for innate but not adaptive immunity.
Inflammasome-mediated disease animal models reveal roles for innate but not adaptive immunity.
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DOI：
10.1016/j.immuni.2009.05.005
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发表时间：
2009-06-19
期刊：
影响因子：
32.4
通讯作者：
Hoffman, Hal M.
中科院分区：
文献类型：
--
作者：
Brydges, Susannah D.;Mueller, James L.;McGeough, Matthew D.;Pena, Carla A.;Misaghi, Amirhossein;Gandhi, Chhavi;Putnam, Chris D.;Boyle, David L.;Firestein, Gary S.;Horner, Anthony A.;Soroosh, Pejman;Watford, Wendy T.;O'Shea, John J.;Kastner, Daniel L.;Hoffman, Hal M.
Cryopyrin（NALP 3）介导炎性体的形成，炎性体是一种负责将pro-IL-1β裂解为其活性形式的蛋白质复合物。cryopyrin基因NLRP 3的突变导致自身炎症性疾病谱：cryopyrin相关周期性综合征（CAPS）。IL-1β在CAPS中的中心作用得到了对IL-1靶向治疗的显著应答的支持。我们开发了两种新的Nlrp 3突变敲入小鼠品系来模拟CAPS，以检查其他炎症介质和适应性免疫应答在先天免疫驱动的疾病中的作用。这些小鼠具有全身性炎症和生长不良，类似于一些人类CAPS患者，并表现出主要由骨髓细胞介导的早期死亡率。将这些突变小鼠与各种敲除背景交配证实了小鼠疾病表型需要完整的炎性小体，仅部分依赖于IL-1β，并且不依赖于T细胞。这些数据表明CAPS是真正的炎性疾病，并为更常见的炎性疾病提供了见解。
Cryopyrin (NALP3) mediates formation of the inflammasome, a protein complex responsible for cleavage of pro-IL-1β to its active form. Mutations in the cryopyrin gene, NLRP3, cause the autoinflammatory disease spectrum: cryopyrin-associated periodic syndromes (CAPS). The central role of IL-1β in CAPS is supported by the remarkable response to IL-1 targeted therapy. We developed two novel Nlrp3 mutant knock-in mouse strains to model CAPS to examine the role of other inflammatory mediators and adaptive immune responses in an innate immune driven disease. These mice had systemic inflammation and poor growth, similar to some human CAPS patients, and demonstrated early mortality, primarily mediated by myeloid cells. Mating these mutant mice to various knock-out backgrounds confirmed the mouse disease phenotype required an intact inflammasome, was only partially dependent on IL-1β, and was independent of T cells. This data suggests CAPS are true inflammasomopathies and provide insight for more common inflammatory disorders.
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DOI：
10.1084/jem.191.2.313
发表时间：
2000-01-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Horai R;Saijo S;Tanioka H;Nakae S;Sudo K;Okahara A;Ikuse T;Asano M;Iwakura Y
通讯作者：
Iwakura Y
DOI：
10.1073/pnas.0611496104
发表时间：
2007-05-08
影响因子：
11.1
作者：
Duncan, Joseph A.;Bergstralht, Daniel T.;Ting, Jenny Pan-Yun
通讯作者：
Ting, Jenny Pan-Yun
影响因子：
3
作者：
Clausen, BE;Burkhardt, C;Förster, I
通讯作者：
Förster, I
影响因子：
3.2
作者：
Kummer, J. Alain;Broekhuizen, Roel;Tschopp, Juerg
通讯作者：
Tschopp, Juerg
影响因子：
9.2
作者：
Lewandoski, M;Wassarman, KM;Martin, GR
通讯作者：
Martin, GR