Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.
Proc Natl Acad Sci U S A. 2010 Oct 26;107(43):18581-6. doi: 10.1073/pnas.1003059107. Epub 2010 Oct 11.
IL-33, a member of the IL-1-related cytokines, is considered to be a proallergic cytokine that is especially involved in Th2-type immune responses. Moreover, like IL-1α, IL-33 has been suggested to act as an "alarmin" that amplifies immune responses during tissue injury. In contrast to IL-1, however, the precise roles of IL-33 in those settings are poorly understood. Using IL-1- and IL-33-deficient mice, we found that IL-1, but not IL-33, played a substantial role in induction of T cell-mediated type IV hypersensitivity such as contact and delayed-type hypersensitivity and autoimmune diseases such as experimental autoimmune encephalomyelitis. Most notably, however, IL-33 was important for innate-type mucosal immunity in the lungs and gut. That is, IL-33 was essential for manifestation of T cell-independent protease allergen-induced airway inflammation as well as OVA-induced allergic topical airway inflammation, without affecting acquisition of antigen-specific memory T cells. IL-33 was significantly involved in the development of dextran-induced colitis accompanied by T cell-independent epithelial cell damage, but not in streptozocin-induced diabetes or Con A-induced hepatitis characterized by T cell-mediated apoptotic tissue destruction. In addition, IL-33-deficient mice showed a substantially diminished LPS-induced systemic inflammatory response. These observations indicate that IL-33 is a crucial amplifier of mucosal and systemic innate, rather than acquired, immune responses.
IL-33，一种白细胞介素-1 相关细胞因子家族的成员，被认为是一种促过敏细胞因子，尤其参与 Th2 型免疫反应。此外，与白细胞介素-1α 类似，IL-33 被认为是一种“警报素”，在组织损伤时放大免疫反应。然而，与白细胞介素-1 不同，IL-33 在这些情况下的确切作用知之甚少。使用白细胞介素-1 和白细胞介素-33 缺陷小鼠，我们发现白细胞介素-1 而不是白细胞介素-33 在诱导 T 细胞介导的 IV 型超敏反应（如接触性和迟发型超敏反应）和自身免疫性疾病（如实验性自身免疫性脑脊髓炎）中发挥了重要作用。然而，最为显著的是，IL-33 对于肺部和肠道中的先天型黏膜免疫至关重要。也就是说，IL-33 对于 T 细胞非依赖性蛋白酶过敏原诱导的气道炎症以及 OVA 诱导的过敏性局部气道炎症的发生是必需的，而不会影响抗原特异性记忆 T 细胞的获得。IL-33 还显著参与了伴有 T 细胞非依赖性上皮细胞损伤的葡聚糖诱导的结肠炎的发生，但不参与由 T 细胞介导的凋亡性组织破坏引起的链脲佐菌素诱导的糖尿病或 Con A 诱导的肝炎。此外，IL-33 缺陷小鼠表现出明显减弱的 LPS 诱导的全身炎症反应。这些观察结果表明，IL-33 是黏膜和全身先天而非获得性免疫反应的关键放大器。
