Th17-to-Tfh plasticity during periodontitis limits disease pathology

Flora A McClure, Kelly Wemyss, Joshua R Cox, Hayley M Bridgeman, Ian E Prise, James I King, Shafqat Jaigirdar, Annie Whelan, Gareth W Jones, John R Grainger, Matthew R Hepworth, Joanne E Konkel*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

Abstract

Th17 cell plasticity is crucial for development of autoinflammatory disease pathology. Periodontitis is a prevalent inflammatory disease where Th17 cells mediate key pathological roles, yet whether they exhibit any functional plasticity remains unexplored. We found that during periodontitis, gingival IL-17 fate-mapped T cells still predominantly produce IL-17A, with little diversification of cytokine production. However, plasticity of IL-17 fate-mapped cells did occur during periodontitis, but in the gingiva draining lymph node. Here, some Th17 cells acquired features of Tfh cells, a functional plasticity that was dependent on IL-6. Notably, Th17-to-Tfh diversification was important to limit periodontitis pathology. Preventing Th17-to-Tfh plasticity resulted in elevated periodontal bone loss that was not simply due to increased proportions of conventional Th17 cells. Instead, loss of Th17-to-Tfh cells resulted in reduced IgG levels within the oral cavity and a failure to restrict the biomass of the oral commensal community. Thus, our data identify a novel protective function for a subset of otherwise pathogenic Th17 cells during periodontitis.

Original languageEnglish
Article numbere20232015
Number of pages16
JournalJournal of Experimental Medicine
Volume221
Issue number8
DOIs
Publication statusPublished - 31 May 2024

Bibliographical note

Publisher Copyright:
© 2024 McClure et al.

Keywords

  • Th17 Cells/immunology
  • Animals
  • Periodontitis/immunology
  • Cell Plasticity/immunology
  • Interleukin-17/metabolism
  • Mice
  • Interleukin-6/metabolism
  • Mice, Inbred C57BL
  • T Follicular Helper Cells/immunology
  • Gingiva/immunology
  • Immunoglobulin G/immunology
  • Alveolar Bone Loss/immunology

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