The cytokines interleukin (IL)-4 and IL-13, signaling via the IL-4 receptor (IL-4R), orchestrate type 2 immunity to helminth infections and toxins. Activation of epithelial and myeloid cells, and a transient neutrophils influx initiates type 2 immune responses, which are dominated by basophils, eosinophils, mast cells, B cell immunoglobulin E production, and type 2 T helper and T follicular helper cells. Interestingly, IL-4 and IL-13 can curtail chemotaxis and several effector functions of neutrophils in mice and humans. This inhibitory role of IL-4 and IL-13 probably developed to limit tissue damage by neutrophils during type 2 immunity where a “weep and sweep” response aims at expulsion and decreased fecundity, instead of killing, of macroparasites. Here, we review when IL-4R signaling cytokines appeared during evolution relative to neutrophils and adaptive immunity. Neutrophil-like granular phagocytes were present in invertebrates throughout the bilaterian clade, but we were unable to find data on IL-4, IL-13, or their receptors in invertebrates. Conversely, vertebrates had both adaptive immunity and IL-4, IL-13, and IL-4Rs, suggesting that type 2 cytokines evolved together with adaptive immunity. Further studies are necessary to determine whether IL-4R signaling in neutrophils was established simultaneously with the appearance of adaptive immunity or later.

通过IL-4受体（IL-4R）发出信号的细胞因子白介素（IL）-4和IL-13协调了对蠕虫感染和毒素的2型免疫。上皮细胞和髓样细胞的激活，以及短暂的嗜中性粒细胞流入引发2型免疫反应，其中以嗜碱性粒细胞，嗜酸性粒细胞，肥大细胞，B细胞免疫球蛋白E产生以及2型T辅助和T滤泡辅助细胞为主。有趣的是，IL-4和IL-13可以抑制小鼠和人类中性粒细胞的趋化性和几种效应子功能。IL-2和IL-13的这种抑制作用可能是为了限制2型免疫过程中嗜中性粒细胞的组织损害，在这种情况下，“扫掠”反应旨在驱逐并降低繁殖力，而不是杀死大寄生虫。这里，我们回顾了相对于嗜中性粒细胞和适应性免疫在进化过程中何时出现IL-4R信号传导细胞因子。中性粒细胞样粒状吞噬细胞存在于整个双侧进化枝的无脊椎动物中，但我们无法找到无脊椎动物中有关IL-4，IL-13或其受体的数据。相反，脊椎动物既具有适应性免疫又具有IL-4，IL-13和IL-4Rs，表明2型细胞因子与适应性免疫一起进化。有必要进行进一步的研究来确定嗜中性粒细胞中的IL-4R信号传导是否与适应性免疫或随后出现同时建立。脊椎动物具有适应性免疫和IL-4，IL-13和IL-4Rs，这表明2型细胞因子与适应性免疫一起进化。有必要进行进一步的研究来确定嗜中性粒细胞中的IL-4R信号传导是否与适应性免疫或随后出现同时建立。脊椎动物具有适应性免疫和IL-4，IL-13和IL-4Rs，这表明2型细胞因子与适应性免疫一起进化。有必要进行进一步的研究来确定嗜中性粒细胞中的IL-4R信号传导是否与适应性免疫或随后出现同时建立。