IL-33-Induced Atopic Dermatitis-Like Inflammation in Mice Is Mediated by Group 2 Innate Lymphoid Cells in Concert with Basophils
IL-33-Induced Atopic Dermatitis-Like Inflammation in Mice Is Mediated by Group 2 Innate Lymphoid Cells in Concert with Basophils
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DOI：
10.1016/j.jid.2019.04.016
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发表时间：
2019-10-01
影响因子：
6.5
通讯作者：
Yamanishi, Kiyofumi
中科院分区：
文献类型：
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作者：
Imai, Yasutomo;Yasuda, Koubun;Yamanishi, Kiyofumi
IL-33 是一种促炎细胞因子，在过敏性疾病中发挥着关键作用。在角蛋白 14 启动子 (IL33tg) 驱动的表达 IL-33 的转基因小鼠中，随着第 2 组先天淋巴细胞 (ILC2) 的激活，特应性皮炎 (AD) 样炎症会自发发生。然而，效应细胞（例如 2 型 T 辅助细胞、ILC2 和嗜碱性粒细胞）如何参与 IL-33 诱导的炎症过程仍不清楚。为了解决这个问题，我们检查了缺乏这些细胞的 IL33tg 小鼠的表型。在缺乏 T 和 B 细胞的 Rag2KO IL33tg 小鼠中，AD 样炎症仍然发生；相比之下，当通过从缺乏ILC2、RAR相关孤儿受体α缺陷的小鼠进行骨髓移植来消除IL33tg小鼠中的ILC2时，AD样炎症的发展几乎被完全抑制。嗜碱性粒细胞在 IL33tg 小鼠发炎的皮肤中积聚，使用抗 Fc epsilon RI α 抗体或 Bas-TRECK 转基因小鼠系统有条件地消耗嗜碱性粒细胞，可减轻 AD 样炎症。在这些嗜碱性粒细胞耗尽的 IL33tg 皮肤中，ILC2 减少，细胞因子和趋化因子（例如 IL-5、IL-13 和 CCL5）减少。从这些结果来看，我们认为 IL-33 诱导的 AD 样炎症依赖于 ILC2 与嗜碱性粒细胞协同介导的先天免疫反应。
IL-33 is a proinflammatory cytokine that plays a pivotal role in allergic disorders. In a transgenic mouse expressing IL-33 driven by a keratin-14 promoter (IL33tg), atopic dermatitis (AD)-like inflammation develops spontaneously with the activation of group 2 innate lymphoid cells (ILC2s). However, it remains unknown how effector cells, such as T helper type 2 cells, ILC2s, and basophils, contribute to the inflammatory process induced by IL-33. To address the question, we examined the phenotype of IL33tg mice lacking each of these cells. AD-like inflammation still developed in Rag2KO IL33tg mice lacking T and B cells; in contrast, when ILC2s were depleted in IL33tg mice via bone marrow transplantation from ILC2-lacking, RAR-related orphan receptor alpha-deficient mice, the development of AD-like inflammation was almost completely suppressed. Basophils were accumulated in the inflamed skin of IL33tg mice, and AD-like inflammation was alleviated by the conditional depletion of basophils using anti-Fc epsilon RI alpha antibodies or a Bas-TRECK transgenic mouse system. In these basophil-depleted IL33tg skins, ILC2s were decreased, and cytokines and chemokines such as IL-5, IL-13, and CCL5 were reduced. From these results, we suggest that IL-33-induced AD-like inflammation is dependent on innate immune responses that are mediated by ILC2s in concert with basophils.