Chemosensory epithelial cells (EpCs) are specialized cells that promote innate type 2 immunity and protective neurally mediated reflexes in the airway. Their effector programs and modes of activation are not fully understood. Here, we define the transcriptional signature of two choline acetyltransferase-expressing nasal EpC populations. They are found in the respiratory and olfactory mucosa and express key chemosensory cell genes including the transcription factor Pou2f3, the cation channel Trpm5, and the cytokine Il25 Moreover, these cells share a core transcriptional signature with chemosensory cells from intestine, trachea and thymus, and cluster with tracheal brush cells (BrCs) independently from other respiratory EpCs, indicating that they are part of the brush/tuft cell family. Both nasal BrC subsets express high levels of transcripts encoding cysteinyl leukotriene (CysLT) biosynthetic enzymes. In response to ionophore, unfractionated nasal BrCs generate CysLTs at levels exceeding that of the adjacent hematopoietic cells isolated from naïve mucosa. Among activating receptors, BrCs express the purinergic receptor P2Y2. Accordingly, the epithelial stress signal ATP and aeroallergens that elicit ATP release trigger BrC CysLT generation, which is mediated by the P2Y2 receptor. ATP- and aeroallergen-elicited CysLT generation in the nasal lavage is reduced in mice lacking Pou2f3, a requisite transcription factor for BrC development. Last, aeroallergen-induced airway eosinophilia is reduced in BrC-deficient mice. These results identify a previously undescribed BrC sensor and effector pathway leading to generation of lipid mediators in response to luminal signals. Further, they suggest that BrC sensing of local damage may provide an important sentinel immune function.

中文翻译：

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气道刷细胞通过 ATP 传感器 P2Y2 产生半胱氨酰白三烯。

化学感应上皮细胞 (EpC) 是一种特殊细胞，可促进先天 2 型免疫和气道中保护性神经介导的反射。它们的效应器程序和激活模式尚未完全了解。在这里，我们定义了两个表达胆碱乙酰转移酶的鼻 EpC 群体的转录特征。它们存在于呼吸道和嗅觉粘膜中，表达关键的化学感应细胞基因，包括转录因子 Pou2f3、阳离子通道 Trpm5 和细胞因子 Il25。此外，这些细胞与来自肠、气管和胸腺的化学感应细胞共享核心转录特征，并且气管刷细胞 (BrC) 与其他呼吸道 EpC 独立地聚集在一起，表明它们是刷/簇细胞家族的一部分。两个鼻 BrC 亚群均表达高水平的编码半胱氨酰白三烯 (CysLT) 生物合成酶的转录本。响应于离子载体，普通鼻 BrC 产生的 CysLT 水平超过从幼稚粘膜分离的邻近造血细胞。在激活受体中，BrC 表达嘌呤能受体 P2Y2。因此，上皮应激信号 ATP 和引起 ATP 释放的气源性过敏原触发 BrC CysLT 生成，这是由 P2Y2 受体介导的。在缺乏 Pou2f3（BrC 发育必需的转录因子）的小鼠中，鼻腔灌洗液中 ATP 和空气过敏原引起的 CysLT 生成减少。最后，BrC 缺陷小鼠中，空气过敏原诱导的气道嗜酸性粒细胞增多减少。这些结果确定了先前未描述的 BrC 传感器和效应器途径，导致响应管腔信号而产生脂质介质。此外，他们认为 BrC 对局部损伤的感知可能提供重要的前哨免疫功能。