Endogenous IL-33 enhances Th2 cytokine production and T-cell responses during allergic airway inflammation

作者：Jennifer Louten, Andrew L. Rankin, Ying Li, Erin E. Murphy, Maribel Beaumont, Christina Moon, Patricia Bourne, Terrill K. McClanahan, Stefan Pflanz, René de Waal Malefyt · 发表于：International Immunology · 年份：2011 · DOI：10.1093/intimm/dxr006 · 被引用次数：132 · 研究领域：IL-33, ST2, and ILC Pathways、Eosinophilic Esophagitis

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.