Gingival transcriptomics of follicular T cell footprints in progressing periodontitis

Abstract

Summary Follicular helper T cells (Tfh) cells have been identified in the circulation and in tertiary lymphoid structures in chronic inflammation. Gingival tissues with periodontitis reflect chronic inflammation, so genomic footprints of Tfh cells should occur in these tissues and may differ related to aging effects. Macaca mulatta were used in a ligature‐induced periodontitis model [adult group (aged 12–23 years); young group (aged 3–7 years)]. Gingival tissue and subgingival microbiome samples were obtained at matched healthy ligature‐induced disease and clinical resolution sites. Microarray analysis examined Tfh genes (n = 54) related to microbiome characteristics documented using 16S MiSeq. An increase in the major transcription factor of Tfh cells, BCL6, was found with disease in both adult and young animals, while master transcription markers of other T cell subsets were either decreased or showed minimal change. Multiple Tfh‐related genes, including surface receptors and transcription factors, were also significantly increased during disease. Specific microbiome patterns were significantly associated with profiles indicative of an increased presence/function of Tfh cells. Importantly, unique microbial complexes showed distinctive patterns of interaction with Tfh genes differing in health and disease and with the age of the animals. An increase in Tfh cell responsiveness occurred in the progression of periodontitis, affected by age and related to specific microbial complexes in the oral microbiome. The capacity of gingival Tfh cells to contribute to localized B cell activation and active antibody responses, including affinity maturation, may be critical for controlling periodontal lesions and contributing to limiting and/or resolving the lesions.

Gingival Transcriptome of Innate Antimicrobial Factors and the Oral Microbiome With Aging and Periodontitis

“…A striking feature of the AMF gene expression patterns was exposed when examining the clustering of the AMF expression in gingival tissues from the various age groups, and in health and disease. Our previous results have supported that the transition from health to disease was a major driving feature of altered gingival gene expression patterns for multiple pathways [27,30,37,38,40,41,[58][59][60][61][62]. While some age differences were observed, the major changes appeared to be disease related.…”

The Role of the Oral Microbiota Related to Periodontal Diseases in Anxiety, Mood and Trauma- and Stress-Related Disorders

“…Pre-clinical studies on periodontal diseases in non-human primates mostly use a ligature-induced periodontitis protocol in Macaca mulatta. To the best of our knowledge there is not documented subsequent development of neuropsychiatric symptoms in these animals with periodontitis; however, recent data have shown that this ligature model induces an increase in follicular helper T cell (Tfh) responsiveness during the progression of periodontitis, which was found to be affected by age and the specific microbial complexes present in the oral microbiome (79). Follicular helper T cells are a specialized subset of CD4+ T cells that play a critical role in protective immunity helping B cells produce antibodies against foreign pathogens.…”

Single-cell and spatially resolved interactomics of tooth-associated keratinocytes in periodontitis

“…8c ). Few papers have described oral tertiary lymphoid structures as a common feature in periodontitis 48 , 49 . We quantified this by the same ROIs using single protein markers and manual thresholding to determine the positivity of by converting 0-255 auxiliary units of fluorescence to a binary classification of either negative (“0”) or positive (“1”; see: Methods).…”