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Gingival Transcriptomics of Follicular T Cell Footprints in Progressing Periodontitis
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  • Jeffrey Ebersole,
  • Sreenatha Kirakodu,
  • Luis Orraca,
  • Janis Gonzalez-Martinez,
  • Octavio Gonzalez
Jeffrey Ebersole
University of Nevada Las Vegas
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Sreenatha Kirakodu
University of Kentucky
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Luis Orraca
University of Puerto Rico Medical Sciences Campus
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Janis Gonzalez-Martinez
University of Puerto Rico
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Octavio Gonzalez
University of Kentucky
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Abstract

Follicular helper T cells (Tfh) cells are generally considered critical in secondary lymphoid tissues; however, they are also 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. Methods: Macaca mulatta monkeys were used in a model of ligature-induced periodontitis [adult group (12-23 years of age); young group (3-7 years)]. Gingival tissue and subgingival microbiome samples were obtained at matched healthy sites, sites during ligature-induced disease, and in samples after clinical resolution. Microarray analysis examined Tfh genes (n=40) and the microbiome samples were examined using 16S MiSeq. Results: An apparent increase in the major transcription factor of Tfh cells, BCL6, was found with disease in both adult and young animals, while the master transcription markers of other T cell subsets were either decreased or showed minimal change. A number of the Tfh related genes, including surface receptors, secreted products and transcription factors were also significantly increased during disease. Unique microbial complexes showed patterns of interactions with Tfh genes that differed in health and disease. Conclusions: An increase in Tfh cell responsiveness occurred later in the progression of periodontitis, affected by age and strongly related to specific microbial complexes. 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.

Peer review status:Published

31 Aug 2020Submitted to Clinical & Experimental Immunology
01 Sep 2020Submission Checks Completed
01 Sep 2020Assigned to Editor
02 Sep 2020Reviewer(s) Assigned
04 Oct 2020Review(s) Completed, Editorial Evaluation Pending
07 Oct 2020Editorial Decision: Revise Major
04 Jan 20211st Revision Received
05 Jan 2021Reviewer(s) Assigned
27 Jan 2021Review(s) Completed, Editorial Evaluation Pending
29 Jan 2021Editorial Decision: Revise Minor
02 Feb 20212nd Revision Received
02 Feb 2021Reviewer(s) Assigned
02 Feb 2021Review(s) Completed, Editorial Evaluation Pending
04 Feb 2021Editorial Decision: Accept
07 Mar 2021Published in Clinical & Experimental Immunology. 10.1111/cei.13584