IL-33trap is a novel IL-33-neutralizing biologic that inhibits allergic airway inflammation.
IL-33trap is a novel IL-33-neutralizing biologic that inhibits allergic airway inflammation.
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DOI：
10.1016/j.jaci.2019.02.028
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发表时间：
2019-07
期刊：
影响因子：
--
通讯作者：
Beyaert R
中科院分区：
文献类型：
--
作者：
Holgado A;Braun H;Van Nuffel E;Detry S;Schuijs MJ;Deswarte K;Vergote K;Haegman M;Baudelet G;Haustraete J;Hammad H;Lambrecht BN;Savvides SN;Afonina IS;Beyaert R
IL-33 作为哮喘和特应性皮炎等广泛炎症性疾病的发展和传播的关键分子参与者的出现，确定了对有效的 IL-33 中和生物制剂的需求。在这里，我们描述了一种名为 IL-33trap 的新型 IL-33 拮抗剂的开发和验证，它将 IL-33 受体 (ST2) 及其共同受体 IL-1 受体辅助蛋白的胞外结构域组合成单个融合蛋白。我们从人类细胞中生产并纯化了重组 IL-33trap，并分析了其在培养细胞和小鼠中的 IL-33 结合亲和力和 IL-33 拮抗活性。 IL-33trap 活性也以对应于天然存在的 IL-33 诱饵受体的重组可溶性 ST2 (sST2) 为基准。最后，我们研究了 IL-33trap 在过敏性气道炎症的 Alternaria alternata 小鼠模型中的作用。在体外，IL-33trap 结合 IL-33，抑制 IL-33 活性比 sST2 强得多。此外，注射 IL-33 后，IL-33trap 可抑制嗜酸性粒细胞浸润、脾肿大以及脾淋巴细胞和肺组织中标志性细胞因子的产生。最后，在过敏原激发时施用 IL-33trap 可抑制急性过敏性气道炎症临床前小鼠模型的炎症反应。 IL-33trap 是一种新型 IL-33 拮抗剂，其性能优于天然 IL-33 诱饵受体，并且在过敏原激发时给予急性过敏性气道炎症的临床前小鼠模型中显示出抗炎活性。
The emergence of IL-33 as a key molecular player in the development and propagation of widespread inflammatory diseases including asthma and atopic dermatitis has established the need for effective IL-33 neutralizing biologics. Here we describe the development and validation of a new antagonist of IL-33, termed IL-33trap, which combines the extracellular domains of the IL-33 receptor (ST2) and its co-receptor IL-1 receptor accessory protein, into a single fusion protein. We produced and purified recombinant IL-33trap from human cells and analyzed its IL-33 binding affinity and IL-33 antagonistic activity in cultured cells and in mice. IL-33trap activity was also benchmarked with a recombinant soluble ST2 (sST2) corresponding to the naturally occurring IL-33 decoy receptor. Finally, we studied the effect of IL-33trap in the Alternaria alternata mouse model of allergic airway inflammation. In vitro, IL-33trap binds IL-33 and inhibits IL-33 activity much stronger than sST2. Furthermore, IL-33trap inhibits eosinophil infiltration, splenomegaly, and the production of signature cytokines in splenic lymphocytes and lung tissue upon IL-33 injection. Finally, administration of IL-33trap at the time of allergen challenge inhibits inflammatory responses in a preclinical mouse model of acute allergic airway inflammation. IL-33trap is a novel IL-33 antagonist that outperforms the natural IL-33 decoy receptor and shows anti-inflammatory activities in a preclinical mouse model of acute allergic airway inflammation when given at the time of allergen challenge.
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DOI：
10.1016/j.jaci.2018.06.002
发表时间：
2018-10
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Godar M;Deswarte K;Vergote K;Saunders M;de Haard H;Hammad H;Blanchetot C;Lambrecht BN
通讯作者：
Lambrecht BN
DOI：
10.1073/pnas.1308651110
发表时间：
2013-09-10
影响因子：
11.1
作者：
Liu, Xi;Hammel, Michal;Wang, Xinquan
通讯作者：
Wang, Xinquan
影响因子：
14.2
作者：
Potaczek, Daniel P.;Garn, Holger;Renz, Harald
通讯作者：
Renz, Harald
影响因子：
16.8
作者：
Elegheert, Jonathan;Bracke, Nathalie;Savvides, Sawas N.
通讯作者：
Savvides, Sawas N.
DOI：
10.1016/j.jaci.2011.10.036
发表时间：
2012-01
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Kim HY;Chang YJ;Subramanian S;Lee HH;Albacker LA;Matangkasombut P;Savage PB;McKenzie AN;Smith DE;Rottman JB;DeKruyff RH;Umetsu DT
通讯作者：
Umetsu DT