The adaptor protein CIKS/Act1 is essential for IL-25-mediated allergic airway inflammation.

The adaptor protein CIKS/Act1 is essential for IL-25-mediated allergic airway inflammation.
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DOI:
10.4049/jimmunol.182.3.1617
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发表时间:
2009-02-01
影响因子:
4.4
通讯作者:
Siebenlist, Ulrich
Siebenlist, Ulrich
中科院分区:
医学2区
文献类型:
--
作者:
Claudio, Estefania;Sonder, Soren Ulrik;Saret, Sun;Carvalho, Gabrielle;Ramalingam, Thirumalai R.;Wynn, Thomas A.;Chariot, Alain;Garcia-Perganeda, Antonio;Leonardi, Antonio;Paun, Andrea;Chen, Amy;Ren, Nina Y.;Wang, Hongshan;Siebenlist, Ulrich

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IL-17是最近发现的辅助性T细胞17型(Th 17)细胞的标志性细胞因子,其在防御细胞外细菌和真菌以及自身免疫性疾病(例如类风湿性关节炎和动物模型中的实验性自身免疫性脑脊髓炎)中突出。IL-25是细胞因子IL-17家族的成员,但与Th 2应答相关,并且可能负交叉调节Th 17/IL-17应答。IL-25可引发气道中的过敏性哮喘样炎症,其包括嗜酸性粒细胞的募集、粘液分泌过多、Th 2细胞因子产生和气道高反应性。我们证明IL-25的这些作用完全依赖于衔接蛋白CIKS(a.k.a. Act 1)。令人惊讶的是,尽管这两种细胞因子引起非常不同的生物反应,但这种衔接子也是传递IL-17信号所必需的。我们确定了CD 11 c+巨噬细胞样肺细胞作为体内IL-25的生理相关靶点。
IL-17 is the signature cytokine of recently discovered T helper type 17 (Th17) cells, which are prominent in defense against extracellular bacteria and fungi as well as in autoimmune diseases, such as rheumatoid arthritis and experimental autoimmune encephalomyelitis in animal models. IL-25 is a member of the IL-17 family of cytokines, but has been associated with Th2 responses instead and may negatively cross-regulate Th17/IL-17 responses. IL-25 can initiate an allergic asthma-like inflammation in the airways, which includes recruitment of eosinophils, mucus hypersecretion, Th2 cytokine production and airways hyperreactivity. We demonstrate that these effects of IL-25 are entirely dependent on the adaptor protein CIKS (a.k.a. Act1). Surprisingly, this adaptor is necessary to transmit IL-17 signals as well, despite the very distinct biologic responses these two cytokines elicit. We identify CD11c+ macrophage-like lung cells as physiologic relevant targets of IL-25 in vivo.
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