Meteorin-like protein/METRNL/Interleukin-41 ameliorates atopic dermatitis-like inflammation.

Autor: Huang D; Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong, China., Liu X; Department of Dermatology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China., Gao X; Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong, China.; Center of Clinical Laboratory Medicine, Zhongda Hospital, Southeast University, Nanjing, China., Choi CK; Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong, China., Giglio G; Bridge Institute of Experimental Tumor Therapy, West German Cancer Center, University Hospital Essen, Essen, Germany.; Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK, partner site Essen) and German Cancer Research Center, DKFZ, Heidelberg, Germany., Farah L; Bridge Institute of Experimental Tumor Therapy, West German Cancer Center, University Hospital Essen, Essen, Germany.; Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK, partner site Essen) and German Cancer Research Center, DKFZ, Heidelberg, Germany., Leung TF; Department of Paediatrics, The Chinese University of Hong Kong, Hong Kong, China., Wong KC; Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong, China., Kan LL; Institute of Chinese Medicine and State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants, The Chinese University of Hong Kong, Hong Kong, China., Chong JW; Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong, China., Meng QJ; Welcome Centre for Cell Matrix Research, Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.; Centre for Biological Timing, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK., Liao J; Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong, China., Cheung PF; Bridge Institute of Experimental Tumor Therapy, West German Cancer Center, University Hospital Essen, Essen, Germany.; Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK, partner site Essen) and German Cancer Research Center, DKFZ, Heidelberg, Germany.; Spatiotemporal tumor heterogeneity, German Cancer Consortium (DKTK), A Partnership Between German Cancer Research Center (DKFZ) and University Hospital, Essen, Germany., Wong CK; Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong, China.; Institute of Chinese Medicine and State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants, The Chinese University of Hong Kong, Hong Kong, China.
Jazyk: angličtina
Zdroj: Allergy [Allergy] 2024 May 10. Date of Electronic Publication: 2024 May 10.
DOI: 10.1111/all.16150
Abstrakt: Background: 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).
Methods: 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.
Results: 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) hi macrophages, dendritic cells, and activated mast cells.
Conclusions: 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.
(© 2024 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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