Department of Immunology, Merck Research Laboratories (formerly Schering-Plough Biopharma), Palo Alto, CA 94304, USA.
Int Immunol. 2011 May;23(5):307-15. doi: 10.1093/intimm/dxr006. Epub 2011 Mar 21.
IL-33 is an IL-1-related cytokine which has been implicated in T(h)2-associated biology and allergic diseases in humans and mice. IL-33 stimulates T(h)2 cells, mast cells, eosinophils, basophils, iNKT cells and circulating CD34(+) stem cells to proliferate and produce pro-allergic cytokines such as IL-5 and IL-13. IL-33 mediates its cytokine effects through a receptor consisting of ST2 and IL-1RAcP. Whereas IL-1RAcP is ubiquitously expressed, ST2 expression is cell-type restricted and determines responsiveness to IL-33. Studies employing ST2-deficient mice have reported variable results on the role of this receptor, and consequently IL-33, with regards to allergic lung inflammation. In this study, we demonstrate that IL-33 is important for allergic lung inflammation. Intra-nasal administration of IL-33 triggered an immediate allergic response in the airways, and more importantly, we show that endogenous IL-33 contributes to airway inflammation and peripheral antigen-specific responses in ovalbumin-induced acute allergic lung inflammation using IL-33-deficient mice. Our results suggest that IL-33 is sufficient and required for severe allergic inflammation in the lung and support the concept of IL-33 as a therapeutic target in allergic lung inflammation.
白细胞介素-33 (IL-33) 是一种白细胞介素-1 相关细胞因子，它与人类和小鼠的 T(h)2 相关生物学和过敏性疾病有关。IL-33 刺激 T(h)2 细胞、肥大细胞、嗜酸性粒细胞、嗜碱性粒细胞、iNKT 细胞和循环 CD34(+) 干细胞增殖，并产生促过敏细胞因子，如 IL-5 和 IL-13。IL-33 通过由 ST2 和 IL-1RAcP 组成的受体发挥其细胞因子作用。虽然 IL-1RAcP 广泛表达，但 ST2 的表达受到细胞类型的限制，并决定对 IL-33 的反应性。采用 ST2 缺陷型小鼠的研究报告了关于该受体以及 IL-33 在过敏性肺炎症中的作用的可变结果。在这项研究中，我们证明了 IL-33 对过敏性肺炎症很重要。鼻内给予 IL-33 会引发气道的即刻过敏反应，更重要的是，我们表明，内源性 IL-33 有助于卵清蛋白诱导的急性过敏性肺炎症中的气道炎症和外周抗原特异性反应，使用 IL-33 缺陷型小鼠。我们的结果表明，IL-33 足以并且需要在肺部引起严重的过敏炎症，并支持将 IL-33 作为过敏性肺炎症的治疗靶点的概念。
