美国康奈尔大学David Artis研究团队发现，白介素33（IL33）通过诱导色氨酸羟化酶1的酶活促进炎性2型先天淋巴样细胞（ILC2）介导的免疫。相关论文3月10日在线发表于《免疫学》。

2型先天淋巴样细胞（ILC2）调节免疫力、炎症和组织稳态。已有研究证明ILC2有两个不同亚型：固有ILC2和炎性ILC2，它们是由蠕虫感染而引起。然而，组织特异性如何调控这两个ILC2亚群及其效应功能仍亟待解决。

研究人员发现IL-33通过诱导色氨酸羟化酶1（Tph1）的酶活促进炎性ILC2s（ILC2INFLAM）的产生。在用IL-33激活或以IL-33依赖性方式感染蠕虫后，ILC2中Tph1的表达上调。淋巴细胞中Tph1条件缺失导致ILC2INFLAM的选择性损伤应答，并增加了对蠕虫感染的易感性。

此外，RNA测序分析揭示了Tph1缺失的ILC2s基因表达发生了改变，包括诱导型T细胞共刺激物（Icos）。

总的来说，这项研究揭示了IL-33、Tph1和ICOS在炎性黏膜屏障促进炎性ILC2反应和2型免疫性方面先前未知的功能。

附：英文原文

Title: Interleukin-33 Induces the Enzyme Tryptophan Hydroxylase 1 to Promote Inflammatory Group 2 Innate Lymphoid Cell-Mediated Immunity

Author: Anne-Laure Flamar, Christoph S.N. Klose, Jesper B. Moeller, Tanel Mahlakiv, Nicholas J. Bessman, Wen Zhang, Saya Moriyama, Vladislava Stokic-Trtica, Lucille C. Rankin, Gregory Garbès Putzel, Hans-Reimer Rodewald, Zhengxiang He, Lili Chen, Sergio A. Lira, Gerard Karsenty, David Artis

Issue&Volume: 2020-03-10

Abstract: Group 2 innate lymphoid cells (ILC2s) regulate immunity, inflammation, and tissuehomeostasis. Two distinct subsets of ILC2s have been described: steady-state naturalILC2s and inflammatory ILC2s, which are elicited following helminth infection. However,how tissue-specific cues regulate these two subsets of ILC2s and their effector functionsremains elusive. Here, we report that interleukin-33 (IL-33) promotes the generationof inflammatory ILC2s (ILC2INFLAM) via induction of the enzyme tryptophan hydroxylase 1 (Tph1). Tph1 expression wasupregulated in ILC2s upon activation with IL-33 or following helminth infection inan 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 sequencinganalysis revealed altered gene expression in Tph1 deficient ILC2s including inducibleT 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.

DOI: 10.1016/j.immuni.2020.02.009

Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30080-7