Gingival transcriptomics of follicular T cell footprints in progressing periodontitis

J. L. Ebersole, S. S. Kirakodu, L. Orraca, J. Gonzalez Martinez, O. A. Gonzalez

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)373-395
Number of pages23
JournalClinical and Experimental Immunology
Volume204
Issue number3
DOIs
StatePublished - Jun 2021

Bibliographical note

Publisher Copyright:
© 2021 British Society for Immunology

Funding

This work was supported by National Institute of Health grant P20GM103538. We express our gratitude to the Caribbean Primate Research Center (CPRC) supported by grant P40RR03640 and the Center for Oral Health Research in the College of Dentistry at the University of Kentucky. The authors thank the Microarray Core of University Kentucky for their invaluable technical assistance and Dr A. Stromberg for initial normalization of the microarray data.

FundersFunder number
Caribbean Primate Research CenterP40RR03640
College of Dentistry
National Institutes of Health (NIH)P20GM103538
National Center for Research ResourcesP40RR003640
University of Kentucky

    Keywords

    • follicular T cells
    • gingiva
    • non-human primates
    • periodontitis

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology

    Fingerprint

    Dive into the research topics of 'Gingival transcriptomics of follicular T cell footprints in progressing periodontitis'. Together they form a unique fingerprint.

    Cite this