IL-33/ST2 enhances MMP-12 expression by macrophages to mediate inflammatory and immune response in IgG4-Related Ophthalmic Disease.

Autor: Ding X; Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, No.639 ZhizaojuRoad, Shanghai 200025, P.R. China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China., Yu Y; Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, No.639 ZhizaojuRoad, Shanghai 200025, P.R. China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China., Su D; Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, No.639 ZhizaojuRoad, Shanghai 200025, P.R. China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China., Lin M; Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, No.639 ZhizaojuRoad, Shanghai 200025, P.R. China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China., Chen M; Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, No.639 ZhizaojuRoad, Shanghai 200025, P.R. China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China., Xing Y; Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, No.639 ZhizaojuRoad, Shanghai 200025, P.R. China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China., Li J; Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, No.639 ZhizaojuRoad, Shanghai 200025, P.R. China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China.
Jazyk: angličtina
Zdroj: Cytokine [Cytokine] 2024 Dec; Vol. 184, pp. 156754. Date of Electronic Publication: 2024 Sep 17.
DOI: 10.1016/j.cyto.2024.156754
Abstrakt: IgG4-Related Ophthalmic Disease (IgG4-ROD) is a chronic autoimmune-mediated fibrotic disease that predominantly affects the lacrimal glands, often leading to loss of function in the involved tissues or organs. Recent studies have demonstrated that MMP-12 is highly expressed in IgG4-ROD and plays a significant role in regulating immune responses. In this study, we reviewed nine patients diagnosed with IgG4-ROD based on clinical manifestations and histological analysis, and we investigated the expression of IL-33/ST2 and MMP-12 in IgG4-ROD lacrimal gland tissues using IHC. We found that IL-33 interacts with its specific receptor ST2, both of which are significantly overexpressed in IgG4-ROD tissues. Additionally, we successfully constructed a mouse model by introducing the Lat Y136F mutation into C57BL/6 mice to mimic IgG4-ROD lacrimal gland involvement, which helped elucidate the mechanisms involved in the induction of MMP-12. Furthermore, immunofluorescence staining confirmed that most MMP-12 + cells were derived from M2 macrophages, and an ELISA assay demonstrated that IL-33 upregulates MMP-12 in IgG4-ROD. Collectively, these data suggest that the IL-33/ST2/MMP-12 signaling pathway is activated in IgG4-ROD, with IL-33/ST2 potentially promoting M2 macrophage polarization and activation to produce MMP-12, which may serve as a novel therapeutic target for IgG4-ROD.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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