IL-33 is a crucial amplifier of innate rather than acquired immunity
IL-33 is a crucial amplifier of innate rather than acquired immunity
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DOI：
10.1073/pnas.1003059107
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发表时间：
2010-10-26
影响因子：
11.1
通讯作者：
Nakae, Susumu
中科院分区：
文献类型：
--
作者：
Oboki, Keisuke;Ohno, Tatsukuni;Nakae, Susumu
IL-33是IL-1相关细胞因子的一员，被认为是一种促变应性细胞因子，尤其参与Th 2型免疫应答。此外，与IL-1 α一样，IL-33被认为是一种“警报素”，在组织损伤期间放大免疫反应。然而，与IL-1相反，IL-33在这些环境中的确切作用知之甚少。使用IL-1和IL-33缺陷小鼠，我们发现IL-1，而不是IL-33，在诱导T细胞介导的IV型超敏反应，如接触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，发挥了重要作用。然而，最值得注意的是，IL-33对肺和肠道中的先天型粘膜免疫很重要。也就是说，IL-33对于T细胞非依赖性蛋白酶变应原诱导的气道炎症以及OVA诱导的过敏性局部气道炎症的表现是必需的，而不影响抗原特异性记忆T细胞的获得。IL-33显着参与葡聚糖诱导的结肠炎伴随T细胞非依赖性上皮细胞损伤的发展，但在链脲佐菌素诱导的糖尿病或Con A诱导的肝炎，其特征在于T细胞介导的凋亡组织破坏。此外，IL-33缺陷型小鼠表现出显著降低的LPS诱导的全身炎症反应。这些观察结果表明，IL-33是粘膜和全身先天性而非获得性免疫应答的关键放大器。
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-1 alpha, 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.