Comparative Metabolomics Reveals the Microenvironment of Common T-Helper Cells and Differential Immune Cells Linked to Unique Periapical Lesions.

Autor:	Altaie AM; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.; Department of Oral and Craniofacial Health Sciences, College of Dental Medicine, University of Sharjah, Sharjah, United Arab Emirates.; Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates., Venkatachalam T; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates., Samaranayake LP; Department of Oral and Craniofacial Health Sciences, College of Dental Medicine, University of Sharjah, Sharjah, United Arab Emirates.; Department of Oral Biosciences, Faculty of Dentistry, University of Hong Kong, Hong Kong, Hong Kong, SAR China., Soliman SSM; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.; Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah, United Arab Emirates., Hamoudi R; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.; Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.; Division of Surgery and Interventional Science, University College London, London, United Kingdom.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2021 Sep 03; Vol. 12, pp. 707267. Date of Electronic Publication: 2021 Sep 03 (Print Publication: 2021).
DOI:	10.3389/fimmu.2021.707267
Abstrakt:	Periapical abscesses, radicular cysts, and periapical granulomas are the most frequently identified pathological lesions in the alveolar bone. While little is known about the initiation and progression of these conditions, the metabolic environment and the related immunological behaviors were examined for the first time to model the development of each pathological condition. Metabolites were extracted from each lesion and profiled using gas chromatography-mass spectrometry in comparison with healthy pulp tissue. The metabolites were clustered and linked to their related immune cell fractions. Clusters I and J in the periapical abscess upregulated the expression of MMP-9, IL-8, CYP4F3, and VEGF, while clusters L and M were related to lipophagy and apoptosis in radicular cyst, and cluster P in periapical granuloma, which contains L-(+)-lactic acid and ethylene glycol, was related to granuloma formation. Oleic acid, 17-octadecynoic acid, 1-nonadecene, and L-(+)-lactic acid were significantly the highest unique metabolites in healthy pulp tissue, periapical abscess, radicular cyst, and periapical granuloma, respectively. The correlated enriched metabolic pathways were identified, and the related active genes were predicted. Glutamatergic synapse (16-20),-hydroxyeicosatetraenoic acids, lipophagy, and retinoid X receptor coupled with vitamin D receptor were the most significantly enriched pathways in healthy control, abscess, cyst, and granuloma, respectively. Compared with the healthy control, significant upregulation in the gene expression of CYP4F3 , VEGF , IL-8 , TLR2 ( P  < 0.0001), and MMP-9 ( P  < 0.001) was found in the abscesses. While IL-12A was significantly upregulated in cysts ( P  < 0.01), IL-17A represents the highest significantly upregulated gene in granulomas ( P  < 0.0001). From the predicted active genes, CIBERSORT suggested the presence of natural killer cells, dendritic cells, pro-inflammatory M1 macrophages, and anti-inflammatory M2 macrophages in different proportions. In addition, the single nucleotide polymorphisms related to IL-10 , IL-12A , and IL-17D genes were shown to be associated with periapical lesions and other oral lesions. Collectively, the unique metabolism and related immune response shape up an environment that initiates and maintains the existence and progression of these oral lesions, suggesting an important role in diagnosis and effective targeted therapy. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Altaie, Venkatachalam, Samaranayake, Soliman and Hamoudi.)
Databáze:	MEDLINE
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