Helminths, allergens, and certain protists induce type 2 immune responses, but the underlying mechanisms of immune activation remain poorly understood. In the small intestine, chemosensing by epithelial tuft cells results in the activation of group 2 innate lymphoid cells (ILC2s), which subsequently drive increased tuft cell frequency. This feedforward circuit is essential for intestinal remodeling and helminth clearance. ILC2 activation requires tuft-cell-derived interleukin-25 (IL-25), but whether additional signals regulate the circuit is unclear. Here, we show that tuft cells secrete cysteinyl leukotrienes (cysLTs) to rapidly activate type 2 immunity following chemosensing of helminth infection. CysLTs cooperate with IL-25 to activate ILC2s, and tuft-cell-specific ablation of leukotriene synthesis attenuates type 2 immunity and delays helminth clearance. Conversely, cysLTs are dispensable for the tuft cell response induced by intestinal protists. Our findings identify an additional tuft cell effector function and suggest context-specific regulation of tuft-ILC2 circuits within the small intestine.

蠕虫，过敏原和某些原生生物诱导2型免疫反应，但对免疫激活的潜在机制仍知之甚少。在小肠中，上皮簇状细胞的化学感应导致第2组先天淋巴样细胞（ILC2s）激活，随后驱动簇状细胞频率增加。该前馈回路对于肠道重塑和清除蠕虫至关重要。ILC2激活需要簇状细胞来源的白介素25（IL-25），但是尚不清楚是否有其他信号调节电路。在这里，我们显示簇状细胞分泌半胱氨酰白三烯（cysLTs），以在蠕虫感染的化学感应后迅速激活2型免疫。CysLT与IL-25协同激活ILC2，和白细胞三烯合成的簇细胞特异性消融减弱了2型免疫力并延迟了蠕虫清除。相反，对于肠道原生生物诱导的簇绒细胞反应，cysLTs是必不可少的。我们的发现确定了一种附加的簇细胞效应子功能，并提出了小肠内簇簇ILC2回路的背景特定调节。