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 (ILC2INFLAM) 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 ILC2INFLAM 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.

中文翻译：

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Interleukin-33 诱导色氨酸羟化酶 1 促进炎症 2 组先天淋巴细胞介导的免疫。

第 2 组先天淋巴细胞 (ILC2) 调节免疫、炎症和组织稳态。已经描述了 ILC2 的两个不同子集：稳态自然 ILC2 和炎症 ILC2，它们是在蠕虫感染后引起的。然而，组织特异性信号如何调节这两个 ILC2 子集及其效应器功能仍然难以捉摸。在此，我们报道白介素 33 (IL-33) 通过诱导色氨酸羟化酶 1 (Tph1) 促进炎症性 ILC2 (ILC2INFLAM) 的产生。IL-33 激活后或蠕虫感染后，ILC2 中的 Tph1 表达以 IL-33 依赖性方式上调。淋巴细胞中 Tph1 的条件性缺失导致 ILC2INFLAM 反应选择性受损，并增加对蠕虫感染的易感性。更远，RNA测序分析揭示了Tph1缺陷型ILC2中基因表达的改变，包括诱导性T细胞共刺激物（Icos）。总的来说，这些数据揭示了 IL-33、Tph1 和 ICOS 在促进粘膜屏障炎症 ILC2 反应和 2 型免疫方面的先前未被认识的功能。