IL-33-induced keratoconjunctivitis is mediated by group 2 innate lymphoid cells in mice
IL-33-induced keratoconjunctivitis is mediated by group 2 innate lymphoid cells in mice
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DOI：
10.1016/j.alit.2022.10.003
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发表时间：
2023-03-31
影响因子：
6.8
通讯作者：
Imai, Yasutomo
中科院分区：
文献类型：
--
作者：
Hosotani, Yuka;Yasuda, Koubun;Imai, Yasutomo
背景资料：白细胞介素-33（IL-33）通过激活第2组先天淋巴样细胞（ILC 2）或辅助性T细胞2（Th 2）诱导2型细胞因子（如IL-5和IL-13）参与2型先天免疫。我们之前报道过，角膜和结膜中过表达IL-33（IL-33 Tg）的小鼠自发出现特应性角结膜炎样炎症。尽管以前的研究，它是不完全了解什么类型的免疫细胞有助于IL-33诱导的keratoconjunctivitis.Methods的疾病过程：缺陷的Th 2细胞，IL-33 Tg小鼠与Rag 2KO小鼠杂交。为了使ILC 2缺陷，IL-33 Tg小鼠接受来自缺乏ILC 2的B6.C3（Cg）-Rorasg/J小鼠的骨髓移植。免疫染色技术用于确定ILC 2在角膜和结膜中的分布位置。我们通过使用单细胞RNA-seq分析来分析来自结膜的ILC 2的转录组。为了研究他克莫司是否通过ILC 2减少2型细胞因子的产生，将ILC 2与他克莫司一起培养，并检查产生精氨酸的ILC 2的百分比。为探讨他克莫司在体内对IL-33诱导的角膜结膜炎的抑制作用，用IL-33 Tg小鼠滴眼液治疗。在Rag 2KO/IL-33 Tg小鼠中自发地发生角膜结膜炎，但在缺乏ILC 2的IL-33 Tg小鼠中角膜结膜炎被消除。ILC 2不是一个均匀的簇，而是一个异质簇。结论：ILC 2在IL-33诱导的小鼠角膜结膜炎中起关键作用。(c)2022日本变态反应学会。由爱思唯尔公司出版。这是一篇开放获取的文章，使用CC BY许可证（http：//creativecommons.org/licenses/by/4.0/）。
Background: Interleukin-33 (IL-33) is involved in type 2 innate immunity by inducing type 2 cytokines, such as IL-5 and IL-13, through the activation of group 2 innate lymphoid cells (ILC2s) or T helper 2 (Th2) cells. We previously reported that mice overexpressing IL-33 (IL-33Tg) in the cornea and conjunctiva spontaneously develop atopic keratoconjunctivitis-like inflammation. Despite previous studies, it is not fully understood what types of immune cells contribute to the disease process of IL-33-induced keratoconjunctivitis.Methods: To defect Th2 cells, IL-33Tg mice were crossed with Rag2KO mice. To defect ILC2s, IL-33Tg mice received bone marrow transplantations from B6.C3(Cg)-Rorasg/J mice that lacked ILC2. Immunostaining techniques were used to determine where ILC2 is distributed in the cornea and conjunctiva. We analyzed the transcriptomes of ILC2 from the conjunctiva by using single-cell RNA-seq analysis. To investigate whether tacrolimus reduces type 2 cytokine production by ILC2, ILC2 was cultured with tacrolimus, and the percentage of cytokine-producing ILC2 was examined. To investigate whether tacrolimus can inhibit IL-33-induced keratoconjunctivitis in vivo, IL-33Tg mice were treated with tacrolimus eye drops.Results: ILC2 infiltrated the conjunctival epithelium and subepithelial tissue. Keratoconjunctivitis developed spontaneously in Rag2KO/IL-33Tg mice, but keratoconjunctivitis was abolished in IL-33Tg mice lacking ILC2. ILC2 was not a uniform cluster but a heterogeneous cluster. Tacrolimus inhibited cytokine production from ILC2s in vitro, and tacrolimus eye drops inhibited keratoconjunctivitis in IL-33Tg mice in vivo.Conclusions: ILC2 plays a pivotal role in IL-33-induced keratoconjunctivitis in mice.(c) 2022 Japanese Society of Allergology. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).