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Disruption of Monocyte and Macrophage Homeostasis in Periodontitis.
Disruption of Monocyte and Macrophage Homeostasis in Periodontitis.
- Source :
-
Frontiers in immunology [Front Immunol] 2020 Feb 26; Vol. 11, pp. 330. Date of Electronic Publication: 2020 Feb 26 (Print Publication: 2020). - Publication Year :
- 2020
-
Abstract
- Monocytes and macrophages are major cellular components of the innate immunity that play essential roles in tissue homeostasis. The contribution of different subsets of monocytes/macrophages to periodontal health and disease has not been fully elucidated. Type 2 diabetes mellitus (T2DM) is a risk factor for periodontitis. We hypothesized that the monocyte/macrophage signaling is perturbed in periodontitis-affected sites versus periodontally healthy sites and that this perturbation plays a critical role in the pathogenesis of periodontitis. Pairs of gingival tissue samples (each from a periodontally healthy and a periodontitis-affected site of the same patient) were harvested from 27 periodontitis patients, with and without T2DM. Each sample was processed to form a single-cell suspension, and a flow-cytometry panel was designed and validated to study monocyte and macrophage phenotypes. In separate experiments, the transcriptional changes associated with a pro-inflammatory phenotype were also examined in monocyte/macrophage subsets obtained from peripheral blood of patients with T2DM versus diabetes-free controls. A significantly higher proportion of intermediate (CD14 <superscript>+</superscript> CD16 <superscript>+</superscript> ) monocytes was observed in periodontitis-affected tissues compared to healthy tissues. These monocytes overexpressed HLA-DR and PDL1 molecules, suggesting their activated inflammatory status. PDL1 increase was specific to intermediate monocytes. The ratio of M1/M2 macrophages was also significantly higher in periodontally affected sites, signifying an imbalance between inflammatory and repair mechanisms. We found a significantly higher expression of PDL1 in overall monocytes and M1 macrophages in periodontitis-affected sites compared to controls. Importantly, we identified a subpopulation of M1 macrophages present in periodontally affected tissues which expressed high levels of CD47, a glycoprotein of the immunoglobulin family that plays a critical role in self-recognition and impairment of phagocytosis. Analysis of the transcriptional landscape of monocytes/macrophages in gingival tissue of T2DM patients with periodontitis revealed a significant disruption in homeostasis toward a proinflammatory phenotype, elevation of pro-inflammatory transcription factors STAT1 and IRF1, and repression of anti-inflammatory JMJD3 in circulating monocytes. Taken together, our results demonstrate disruption of myeloid-derived cell homeostasis in periodontitis, with or without T2DM, and highlight a potentially significant role of these cell types in its pathogenesis. The impact of macrophage and monocyte signaling pathways on the pathobiology of periodontitis should be further evaluated.<br /> (Copyright © 2020 Almubarak, Tanagala, Papapanou, Lalla and Momen-Heravi.)
- Subjects :
- B7-H1 Antigen biosynthesis
B7-H1 Antigen genetics
CD47 Antigen biosynthesis
CD47 Antigen genetics
Cells, Cultured
Diabetes Mellitus, Type 2 complications
Diabetes Mellitus, Type 2 immunology
GPI-Linked Proteins analysis
Gingiva immunology
Gingiva pathology
Gingival Hemorrhage etiology
HLA-DR Antigens biosynthesis
HLA-DR Antigens genetics
Homeostasis
Humans
Immunity, Innate
Inflammation
Lipopolysaccharide Receptors analysis
Macrophages classification
Macrophages metabolism
Monocytes metabolism
Periodontitis complications
Receptors, IgG analysis
Signal Transduction
Transcription Factors metabolism
Macrophages immunology
Monocytes immunology
Periodontitis immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1664-3224
- Volume :
- 11
- Database :
- MEDLINE
- Journal :
- Frontiers in immunology
- Publication Type :
- Academic Journal
- Accession number :
- 32210958
- Full Text :
- https://doi.org/10.3389/fimmu.2020.00330