Interleukin-33 Induces the Enzyme Tryptophan Hydroxylase 1 to Promote Inflammatory Group 2 Innate Lymphoid Cell-Mediated Immunity
Interleukin-33 Induces the Enzyme Tryptophan Hydroxylase 1 to Promote Inflammatory Group 2 Innate Lymphoid Cell-Mediated Immunity
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DOI：
10.1016/j.immuni.2020.02.009
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发表时间：
2020-04-14
期刊：
影响因子：
32.4
通讯作者：
Artis, David
中科院分区：
文献类型：
--
作者：
Flamar, Anne-Laure;Klose, Christoph S. N.;Artis, David
第2组先天淋巴样细胞（ILC 2）调节免疫，炎症和组织稳态。已经描述了ILC 2的两个不同的子集：稳态天然ILC 2和炎性ILC 2，其在蠕虫感染后引起。然而，组织特异性的线索如何调节ILC 2的这两个子集及其效应器功能仍然难以捉摸。在这里，我们报告说，白细胞介素-33（IL-33）促进炎症ILC 2（ILC 2（INFLAM））通过诱导酶色氨酸羟化酶1（Tph 1）的产生。IL-33激活或蠕虫感染后，IL-2s中Tph 1表达上调，IL-33依赖性的方式。淋巴细胞中Tph 1的条件性缺失导致ILC 2（INFLAM）反应的选择性损害和对蠕虫感染的易感性增加。此外，RNA测序分析揭示了Tph 1缺陷ILC 2中改变的基因表达，包括诱导型T细胞共刺激因子（Icos）。总的来说，这些数据揭示了IL-33，Tph 1和ICOS在促进炎症ILC 2反应和粘膜屏障2型免疫中的先前未被认识的功能。
Group 2 innate lymphoid cells (ILC2s) regulate immunity, inflammation, and tissue homeostasis. Two distinct subsets of ILC2s have been described: steady-state natural ILC2s and inflammatory ILC2s, which are elicited following helminth infection. However, how tissue-specific cues regulate these two subsets of ILC2s and their effector functions remains elusive. Here, we report that interleukin-33 (IL-33) promotes the generation of inflammatory ILC2s (ILC2(INFLAM)) via induction of the enzyme tryptophan hydroxylase 1 (Tph1). Tph1 expression was upregulated in ILC2s upon activation with IL-33 or following helminth infection in an IL-33-dependent manner. Conditional deletion of Tph1 in lymphocytes resulted in selective impairment of ILC2(INFLAM) responses and increased susceptibility to helminth infection. Further, RNA sequencing analysis revealed altered gene expression in Tph1 deficient ILC2s including inducible T cell co-stimulator (Icos). Collectively, these data reveal a previously unrecognized function for IL-33, Tph1, and ICOS in promoting inflammatory ILC2 responses and type 2 immunity at mucosal barriers.