Decoding the role of macrophages in periodontitis and type 2 diabetes using single‐cell RNA‐sequencing
- 15 January 2022
- journal article
- research article
- Published by Wiley in The FASEB Journal
- Vol. 36 (2), e22136
- https://doi.org/10.1096/fj.202101198r
Abstract
Macrophages are resident myeloid cells in the gingival tissue which control homeostasis and play a pivotal role in orchestrating the immune response in periodontitis. Cell heterogeneity and functional phenotypes of macrophage subpopulations in periodontitis remain elusive. Here, we isolated gingival tissue from periodontitis-affected and healthy sites of patients with and without type 2 diabetes mellitus (T2DM). We then used single-cell RNA-sequencing (scRNA-seq) to define the heterogeneity of tissue-resident macrophages in gingival tissue in health vs. periodontitis. scRNA-seq demonstrated an unforeseen gene expression heterogeneity among macrophages in periodontitis and showed transcriptional and signaling heterogeneity of identified subsets in an independent cohort of patients with periodontitis and T2DM. Our bioinformatic inferences indicated divergent expression profiles in macrophages driven by transcriptional regulators CIITA, RELA, RFX5, and RUNX2. Macrophages in periodontitis expressed both pro-inflammatory and anti-inflammatory markers and their polarization was not mutually exclusive. The majority of macrophages in periodontitis expressed the monocyte lineage marker CD14, indicating their bone marrow lineage. We also found high expression and activation of RELA, a subunit of the NF-κB transcription factor complex, in gingival macrophages of periodontitis patients with T2DM. Our data suggested that heterogeneity and hyperinflammatory activation of macrophages may be relevant to the pathogenesis and outcomes of periodontitis, and may be further augmented in patients with T2DM.Keywords
Funding Information
- National Institute of Dental and Craniofacial Research (DE029546‐01)
- National Center for Advancing Translational Sciences (KL2TR001874)
This publication has 47 references indexed in Scilit:
- Diabetes mellitus and periodontitis: a tale of two common interrelated diseasesNature Reviews Endocrinology, 2011
- Nuclear factor-κB p50 subunits in chronic periodontitis and Porphyromonas gingivalis lipopolysaccharide-pulsed dendritic cellsAnnals of the New York Academy of Sciences, 2010
- Quantitative imaging assay for NF-κB nuclear translocation in primary human macrophagesJournal of Immunological Methods, 2008
- Role of the MHC2TA gene in autoimmune diseasesAnnals Of The Rheumatic Diseases, 2007
- Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profilesProceedings of the National Academy of Sciences of the United States of America, 2005
- The two NF-κB activation pathways and their role in innate and adaptive immunityTrends in Immunology, 2004
- Over-expression of the ribosomal protein L36a gene is associated with cellular proliferation in hepatocellular carcinomaJournal of Hepatology, 2004
- Are there HLA combinations typical supporting for or making resistant against aggressive and/or chronic periodontitis?Journal of Periodontal Research, 2003
- NF-κB regulation in the immune systemNature Reviews Immunology, 2002
- Mice Lacking the MHC Class II Transactivator (CIITA) Show Tissue-Specific Impairment of MHC Class II ExpressionImmunity, 1996