IL-1 receptor accessory protein is essential for IL-33-induced activation of T lymphocytes and mast cells
IL-1 receptor accessory protein is essential for IL-33-induced activation of T lymphocytes and mast cells
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DOI：
10.1073/pnas.0705939104
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发表时间：
2007-11-20
影响因子：
11.1
通讯作者：
Martin, Michael U.
中科院分区：
文献类型：
--
作者：
Ali, Shafaqat;Hubert, Michael;Martin, Michael U.
缺乏IL-1受体辅助蛋白（IL-1 RAcP）消除小鼠胸腺瘤克隆EL-4 D 6/76细胞对IL-33和IL-1的反应。用全长IL-1 RAcP重建足以恢复对IL-33和IL-1的响应性。IL-33以IL-1 RAcP依赖性方式激活IL-1受体相关激酶-1、cJun-N-末端激酶和NF-κ B通路，并导致IL-2释放。IL-33能够诱导骨髓源性（BMD）肥大细胞中促炎细胞因子的释放，表明IL-33除了先前描述的适应性应答中的Th 2偏斜特性之外，还可能具有与其亲属IL-1和IL-18类似的促炎潜力。用中和抗体4C 5阻断鼠IL-1 RAcP可抑制小鼠胸腺瘤细胞和BMD肥大细胞对IL-33的应答。膜结合或可溶形式的IL-1 RAcP和IL-33 R α链的相互作用取决于IL-33的存在，如通过共免疫沉淀测定所证明的。这些数据表明IL-1 RAcP对于IL-33信号传导是必不可少的。此外，他们认为IL-1 RAcP被IL-1受体家族的一个以上的α链使用，因此可能类似于该家族的共同β链。
Lack of the IL-1 receptor accessory protein (IL-1RAcP) abrogates responses to IL-33 and IL-1 in the mouse thymoma clone EL-4 D6/76 cells. Reconstitution with full-length lL-1RAcP is sufficient to restore responsiveness to IL-33 and IL-1. IL-33 activates IL-1 receptor-associated kinase-1, cJun-N-terminal kinase, and the NF-kappa B pathway in an IL-1RAcP-dependent manner and results in IL-2 release. IL-33 is able to induce the release of proinflammatory cytokines in bone marrow-derived (BMD) mast cells, indicating that IL-33 may have a proinflammatory potential like its relatives IL-1 and IL-18, in addition to its Th2-skewing properties in the adaptive response described previously. Blocking of murine IL-1RAcP with the neutralizing antibody 4C5 inhibits response of mouse thymoma cells and BMD mast cells to IL-33. The interaction of either membrane-bound or soluble forms of lL-1RAcP and IL-33R alpha-chain depends on the presence of IL-33, as demonstrated by coimmuno-precipitation assays. These data demonstrate that IL-1RAcP is indispensable for IL-33 signaling. Furthermore, they suggest that IL-1RAcP is used by more than one alpha-chain of the IL-1 receptor family and thus may resemble a common beta-chain of that family.