Analysis of Inflammatory and Homeostatic Roles of Tissue-resident Macrophages in the Progression of Cholesteatoma by RNA-Seq. (18th August 2021)

• Record Type: Journal Article
• Authors: Fang, Lian; Chen, Lin; Lin, Bi; Han, Liang; Zhu, Kaiquan; Song, Qifa
• Is Part Of: Immunological investigations. Volume 50:Number 6(2021)
• Page Start: 609
• Page End: 621
• Publication Date: 2021-08-18
• Subjects: Middle ear -- cholesteatoma -- tissue-resident macrophages (TRMØ) -- RNA-Seq -- gene expression; Immunology -- Periodicals; Immunochemistry -- Periodicals; Cellular immunity -- Periodicals; Communicable diseases -- Periodicals; 616.079
• DOI: 10.1080/08820139.2020.1781161
• Languages: English
• ISSNs: 0882-0139

Abstract

ABSTRACT: Background: Tissue-resident macrophages (TRMØs) can act as innate-immune sentinels to protect body against microbe invaders and stimulating materials such as cholesterol crystals in cholesteatoma, as well as to preserve tissue integrity by cleaning unwanted cellular debris. Methods: TRMØs in the incised middle ear tissues were obtained from the patients with cholesteatoma as an experimental group and the patients without cholesteatoma as a control group. Differential gene expression profiling of TRMØs was conducted between two groups by analyzing GO processes, KEGG and GSEA pathways of inflammation, tissue repair and homeostasis. Results: The current study showed that 145 of 7060 genes were significantly up-regulated (logFC>2 and FDR <0.05) when compared with the patients without cholesteatoma. GO process, GSEA and Cytoscape analysis of the over-expressed genes illustrated the boosted inflammatory and anti-infection functions of TRMØs existed neutrophil function, leukocyte migration, and adaptive immune response involved receptors and signaling pathways. Whereas the homeostasis and repair functions of TRMØs were affected from up-regulated genes, such as over-expressed keratin-13 that helped form the outer keratinising squamous epithelial layer, and over-expressed MMPs that activated the extracellular matrix molecules to promote inflammation and disturb tissue remodeling. Additionally, 74 down-regulated genes (logFC<-2 and FDR <0.05) also affected the homeostasis and repair functions by affecting extracelluar matrix structure and contractile fibres in TRMØs. Conclusions: The cellular and molecular levels in cholesteatoma is attributable to chronic infection and several disturbed cellular biological processes involving cell integrity and tissue remodeling.