Huang Danqi, Liu Xiuting, Gao Xun, Choi Chun Kit, Giglio Giovanni, Farah Luay, Leung Ting-Fan, Wong Katie Ching-Yau, Kan Lea Ling-Yu, Chong Jeffrey Wing-Heung, Meng Qing-Jun, Liao Jinyue, Cheung Phyllis Fung-Yi, Wong Chun-Kwok
Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong, China.
Department of Dermatology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
Allergy. 2025 Feb;80(2):474-488. doi: 10.1111/all.16150. Epub 2024 May 10.
Meteorin-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).
METRNL 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.
METRNL 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) macrophages, dendritic cells, and activated mast cells.
METRNL 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.
类陨石蛋白（METRNL）/白细胞介素-41（IL-41）是一种新型的免疫分泌细胞因子/肌动蛋白，参与多种炎症性疾病。然而，METRNL如何对皮肤炎症发挥其调节特性仍不清楚。本研究旨在阐明METRNL在特应性皮炎（AD）中的功能和调节机制。
测定AD患者皮肤和血清样本中的METRNL水平，并随后在维生素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测序和RNA测序鉴定METRNL活性的细胞靶点。
与健康对照相比，AD患者皮损和血清中的METRNL显著上调（p < 0.05）。反复暴露于MC903后，AD模型小鼠双耳和血清中的METRNL水平均升高。给予重组小鼠METRNL蛋白（rmMETRNL）可改善小鼠过敏性皮肤炎症和AD的特征，而阻断METRNL信号则导致相反的结果。METRNL增强β-连环蛋白的激活，限制Th2相关分子的表达，这些分子吸引精氨酸酶-1（Arg1）巨噬细胞、树突状细胞和活化肥大细胞的积累。
METRNL可与KIT受体结合，随后通过抑制免疫细胞的扩增来减轻AD的过敏性炎症，并通过调节活性WNT通路分子β-连环蛋白的水平来下调炎症基因表达。
