BACKGROUND Psychological stress can exacerbate the development of allergies; however, the underlying mechanisms remain poorly understood. IgE-mediated cutaneous allergic inflammation (IgE-CAI) is a basophil-dependent skin allergy with eosinophil infiltration at inflammatory sites. Its resolution involves anti-inflammatory programmed death ligand 2 (PD-L2)-positive macrophages. OBJECTIVE This study sought to elucidate the cellular and molecular mechanisms by which psychological stress exacerbates IgE-CAI. METHODS Neural tissue involved in stress-induced IgE-CAI exacerbation was identified by performing denervation and brain destruction experiments in mice. Immune cell transplantation, RNA sequencing, flow cytometry, and ELISA were used to identify and characterize immune cells with stress-altered functioning, followed by identification of key factors involved in IgE-CAI exacerbation. RESULTS Stress-induced exacerbation of IgE-CAI was found to be sympathetic and β2-adrenergic receptor (Adrb2)-dependent. Adoptive transfer experiments revealed that stress diminished the anti-inflammatory functions of PD-L2-positive macrophages through Adrb2, exacerbating the inflammation. RNA sequencing analysis indicated that PD-L2-positive macrophages in stressed mice exhibit reduced expression of efferocytosis-related genes, including Gas6 and MerTK. Consequently, the efferocytic capacity of these macrophages decreased, resulting in increased numbers of dead cells in the lesions. The exacerbation and upregulation of Ccl24 expression in IgE-CAI skin lesions were countered by a Caspase-1 inhibitor. CONCLUSIONS Psychological stress diminishes the efferocytotic capacity of PD-L2-positive macrophages, causing an accumulation of dead cells. This, in turn, heightens eosinophil infiltration through Caspase-1-dependent production of CCL24, exacerbating IgE-CAI.

中文翻译：

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在皮肤过敏性炎症中，经历压力的单核细胞/巨噬细胞通过 β2-肾上腺素能受体失去抗炎功能。


背景 心理压力会加剧过敏的发展;然而，对其潜在机制仍然知之甚少。IgE 介导的皮肤过敏性炎症 （IgE-CAI） 是一种嗜碱性粒细胞依赖性皮肤过敏，炎症部位嗜酸性粒细胞浸润。其分辨率涉及抗炎程序性死亡配体 2 （PD-L2） 阳性巨噬细胞。目的 本研究试图阐明心理应激加剧 IgE-CAI 的细胞和分子机制。方法 通过在小鼠中进行去神经支配和脑破坏实验来鉴定参与应激诱导的 IgE-CAI 恶化的神经组织。免疫细胞移植、RNA 测序、流式细胞术和 ELISA 用于鉴定和表征应激功能改变的免疫细胞，然后鉴定参与 IgE-CAI 恶化的关键因素。结果 发现应激诱导的 IgE-CAI 恶化是交感神经和 β2-肾上腺素能受体 （Adrb2） 依赖性的。过继转移实验显示，应激通过 Adrb2 降低了 PD-L2 阳性巨噬细胞的抗炎功能，加剧了炎症。RNA 测序分析表明，应激小鼠中 PD-L2 阳性巨噬细胞表现出胞吐相关基因（包括 Gas6 和 MerTK）的表达降低。因此，这些巨噬细胞的泡糖细胞能力降低，导致病变中死细胞的数量增加。Caspase-1 抑制剂抵消了 IgE-CAI 皮肤病变中 Ccl24 表达的恶化和上调。结论 心理应激降低了 PD-L2 阳性巨噬细胞的泡血细胞能力，导致死细胞积累。 这反过来又增加了嗜酸性粒细胞通过 Caspase-1 依赖性产生 CCL24 的浸润，从而加剧了 IgE-CAI。