BackgroundMeteorin‐like protein (METRNL)/Interleukin‐41 (IL‐41) is a novel immune‐secreted cytokine/myokine involved in several inflammatory diseases. However, how METRNL exerts its regulatory properties on skin inflammation remains elusive. This study aims to elucidate the functionality and regulatory mechanism of METRNL in atopic dermatitis (AD).MethodsMETRNL levels were determined in skin and serum samples from patients with AD and subsequently verified in the vitamin D3 analogue MC903‐induced AD‐like mice model. The cellular target of METRNL activity was identified by multiplex immunostaining, single‐cell RNA‐seq and RNA‐seq.ResultsMETRNL was significantly upregulated in lesions and serum of patients with dermatitis compared to healthy controls (p <.05). Following repeated MC903 exposure, AD model mice displayed elevated levels of METRNL in both ears and serum. Administration of recombinant murine METRNL protein (rmMETRNL) ameliorated allergic skin inflammation and hallmarks of AD in mice, whereas blocking of METRNL signaling led to the opposite. METRNL enhanced β‐Catenin activation, limited the expression of Th2‐related molecules that attract the accumulation of Arginase‐1 (Arg1)hi macrophages, dendritic cells, and activated mast cells.ConclusionsMETRNL can bind to KIT receptor and subsequently alleviate the allergic inflammation of AD by inhibiting the expansion of immune cells, and downregulating inflammatory gene expression by regulating the level of active WNT pathway molecule β‐Catenin.

中文翻译：

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镍纹蛋白样蛋白/METRNL/白细胞介素-41 可改善特应性皮炎样炎症

背景镍纹蛋白样蛋白（METRNL）/白细胞介素-41（IL-41）是一种新型免疫分泌细胞因子/肌因子，参与多种炎症性疾病。然而，METRNL 如何发挥其对皮肤炎症的调节作用仍不清楚。本研究旨在阐明 METRNL 在特应性皮炎 (AD) 中的功能和调节机制。方法在 AD 患者的皮肤和血清样本中测定 METRNL 水平，随后在维生素 D3 类似物 MC903 诱导的 AD 样小鼠模型中进行验证。通过多重免疫染色、单细胞 RNA-seq 和 RNA-seq 鉴定了 METRNL 活性的细胞靶标。结果与健康对照相比，皮炎患者的皮损和血清中 METRNL 显着上调（p<.05)。反复接触 MC903 后，AD 模型小鼠的耳朵和血清中 METRNL 水平升高。施用重组鼠 METRNL 蛋白 (rmMETRNL) 可改善小鼠的过敏性皮肤炎症和 AD 特征，而阻断 METRNL 信号传导则会导致相反的结果。 METRNL 增强 β-Catenin 激活，限制 Th2 相关分子的表达，从而吸引精氨酸酶-1（精氨酸1）你好结论 METRNL可与KIT受体结合，抑制免疫细胞的扩增，并通过调节活性WNT通路分子β-Catenin的水平下调炎症基因表达，从而减轻AD的过敏性炎症。