PMID- 32210958 OWN - NLM STAT- MEDLINE DCOM- 20210305 LR - 20220902 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 11 DP - 2020 TI - Disruption of Monocyte and Macrophage Homeostasis in Periodontitis. PG - 330 LID - 10.3389/fimmu.2020.00330 [doi] LID - 330 AB - 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(+)CD16(+)) 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. CI - Copyright (c) 2020 Almubarak, Tanagala, Papapanou, Lalla and Momen-Heravi. FAU - Almubarak, Abdulrahman AU - Almubarak A AD - Division of Periodontics, Section of Oral, Diagnostic and Rehabilitation Sciences, Columbia University College of Dental Medicine, New York, NY, United States. FAU - Tanagala, Kranthi Kiran Kishore AU - Tanagala KKK AD - Division of Periodontics, Section of Oral, Diagnostic and Rehabilitation Sciences, Columbia University College of Dental Medicine, New York, NY, United States. FAU - Papapanou, Panos N AU - Papapanou PN AD - Division of Periodontics, Section of Oral, Diagnostic and Rehabilitation Sciences, Columbia University College of Dental Medicine, New York, NY, United States. FAU - Lalla, Evanthia AU - Lalla E AD - Division of Periodontics, Section of Oral, Diagnostic and Rehabilitation Sciences, Columbia University College of Dental Medicine, New York, NY, United States. FAU - Momen-Heravi, Fatemeh AU - Momen-Heravi F AD - Division of Periodontics, Section of Oral, Diagnostic and Rehabilitation Sciences, Columbia University College of Dental Medicine, New York, NY, United States. AD - Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY, United States. LA - eng GR - P30 CA013696/CA/NCI NIH HHS/United States GR - R03 DE029546/DE/NIDCR NIH HHS/United States GR - UL1 TR001873/TR/NCATS NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20200226 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (B7-H1 Antigen) RN - 0 (CD14 protein, human) RN - 0 (CD274 protein, human) RN - 0 (CD47 Antigen) RN - 0 (CD47 protein, human) RN - 0 (FCGR3B protein, human) RN - 0 (GPI-Linked Proteins) RN - 0 (HLA-DR Antigens) RN - 0 (Lipopolysaccharide Receptors) RN - 0 (Receptors, IgG) RN - 0 (Transcription Factors) SB - IM MH - B7-H1 Antigen/biosynthesis/genetics MH - CD47 Antigen/biosynthesis/genetics MH - Cells, Cultured MH - Diabetes Mellitus, Type 2/complications/immunology MH - GPI-Linked Proteins/analysis MH - Gingiva/immunology/pathology MH - Gingival Hemorrhage/etiology MH - HLA-DR Antigens/biosynthesis/genetics MH - Homeostasis MH - Humans MH - Immunity, Innate MH - Inflammation MH - Lipopolysaccharide Receptors/analysis MH - Macrophages/classification/*immunology/metabolism MH - Monocytes/*immunology/metabolism MH - Periodontitis/complications/*immunology MH - Receptors, IgG/analysis MH - Signal Transduction MH - Transcription Factors/metabolism PMC - PMC7067288 OTO - NOTNLM OT - CD47 OT - diabetes OT - macrophages OT - monocytes OT - periodontitis EDAT- 2020/03/27 06:00 MHDA- 2021/03/06 06:00 PMCR- 2020/01/01 CRDT- 2020/03/27 06:00 PHST- 2019/10/16 00:00 [received] PHST- 2020/02/10 00:00 [accepted] PHST- 2020/03/27 06:00 [entrez] PHST- 2020/03/27 06:00 [pubmed] PHST- 2021/03/06 06:00 [medline] PHST- 2020/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2020.00330 [doi] PST - epublish SO - Front Immunol. 2020 Feb 26;11:330. doi: 10.3389/fimmu.2020.00330. eCollection 2020.