Type-2 immunity is characterised by interleukin (IL)-4, IL-5 and IL-13, eosinophilia, mucus production, IgE, and alternatively activated macrophages (AAM). However, despite the lack of neutrophil chemoattractants such as CXCL1, neutrophils, a feature of type-1 immunity, are observed in type-2 responses. Consequently, alternative mechanisms must exist to ensure that neutrophils can contribute to type-2 immune reactions without escalation of deleterious inflammation. We now demonstrate that type-2 immune-associated neutrophil infiltration is regulated by the mouse RNase A homologue, eosinophil-associated ribonuclease 11 (Ear11), which is secreted by AAM downstream of IL-25-stimulated ILC2. Transgenic overexpression of Ear11 resulted in tissue neutrophilia, whereas Ear11-deficient mice have fewer resting tissue neutrophils, whilst other type-2 immune responses are not impaired. Notably, administration of recombinant mouse Ear11 increases neutrophil motility and recruitment. Thus, Ear11 helps maintain tissue neutrophils at homoeostasis and during type-2 reactions when chemokine-producing classically activated macrophages are infrequently elicited.

2 型免疫的特征在于白细胞介素 (IL)-4、IL-5 和 IL-13、嗜酸性粒细胞增多、粘液产生、IgE 和交替激活的巨噬细胞 (AAM)。然而，尽管缺乏 CXCL1 等嗜中性粒细胞趋化因子，但在 2 型反应中仍观察到嗜中性粒细胞（1 型免疫的一个特征）。因此，必须存在替代机制来确保嗜中性粒细胞可以促进 2 型免疫反应，而不会加剧有害炎症。我们现在证明 2 型免疫相关中性粒细胞浸润受小鼠 RNase A 同系物嗜酸性粒细胞相关核糖核酸酶 11 (Ear11) 的调节，它由 IL-25 刺激的 ILC2 下游的 AAM 分泌。Ear11 的转基因过表达导致组织中性粒细胞增多，而 Ear11 缺陷小鼠的静息组织中性粒细胞较少，而其他 2 型免疫反应未受损。值得注意的是，重组小鼠 Ear11 的施用增加了嗜中性粒细胞的运动和募集。因此，Ear11 有助于维持组织嗜中性粒细胞的稳态和在 2 型反应期间，当产生趋化因子的经典激活的巨噬细胞很少被引出时。