美国哈佛医学院Joshua A. Boyce及其团队的研究发现，巨细胞通过前列腺素E2（PGE2）诱导的可溶性ST2调控肺部2型炎症（T2I）。该研究于2024年5月30日发表于国际学术期刊《免疫》杂志上。

研究人员证明，前列腺素E2能诱导产生sST2，从而限制肺部T2I特征。PGE2缺乏的小鼠显示出sST2减少。在患有严重呼吸道T2I的人体中，尿液PGE2代谢物与血清sST2相关。在小鼠中，PGE2可诱导巨细胞（MCs）分泌sST2。缺乏巨细胞、巨细胞ST2 表达减少或巨细胞E类前列腺素（EP）2 受体缺乏的小鼠显示出肺部sST2浓度降低和严重的T2I。

在MCs表达PGE2或ST2缺陷的小鼠中回补重组的sST2可使T2I回到控制水平。PGE2缺乏也逆转了由MCs表达ST2缺乏小鼠的高炎症表型。因此，PGE2可通过MC衍生的sST2抑制T2I，这解释了在低PGE2时观察到的严重T2I表型。

据悉，严重哮喘和鼻窦疾病是由2型炎症引起的，由白细胞介素（IL）-33 通过其膜结合受体ST2传递信号。可溶性（s）ST2能减少IL-33可及性并限制T2I，但人们对其调控机制知之甚少。

附：英文原文

Title: Mast cells control lung type 2 inflammation via prostaglandin E2-driven soluble ST2

Author: Kinan Alhallak, Jun Nagai, Kendall Zaleski, Sofia Marshall, Tamara Salloum, Tahereh Derakhshan, Hiroaki Hayashi, Chunli Feng, Radomir Kratchmarov, Juying Lai, Virinchi Kuchibhotla, Airi Nishida, Barbara Balestrieri, Tanya Laidlaw, Daniel F. Dwyer, Joshua A. Boyce

Issue&Volume: 2024-05-30

Abstract: Severe asthma and sinus disease are consequences of type 2 inflammation (T2I), mediatedby interleukin (IL)-33 signaling through its membrane-bound receptor, ST2. Soluble(s)ST2 reduces available IL-33 and limits T2I, but little is known about its regulation.We demonstrate that prostaglandin E2 (PGE2) drives production of sST2 to limit features of lung T2I. PGE2-deficient mice display diminished sST2. In humans with severe respiratory T2I, urinaryPGE2 metabolites correlate with serum sST2. In mice, PGE2 enhanced sST2 secretion by mast cells (MCs). Mice lacking MCs, ST2 expression byMCs, or E prostanoid (EP)2 receptors by MCs showed reduced sST2 lung concentrations and strong T2I. RecombinantsST2 reduced T2I in mice lacking PGE2 or ST2 expression by MCs back to control levels. PGE2 deficiency also reversed the hyperinflammatory phenotype in mice lacking ST2 expressionby MCs. PGE2 thus suppresses T2I through MC-derived sST2, explaining the severe T2I observed in low PGE2 states.

DOI: 10.1016/j.immuni.2024.05.003

Source: https://www.cell.com/immunity/abstract/S1074-7613(24)00254-1