Th17-to-Tfh plasticity during periodontitis limits disease pathology

J Exp Med. 2024 Aug 5;221(8):e20232015. doi: 10.1084/jem.20232015. Epub 2024 May 31.

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.

MeSH terms

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

Substances

  • Interleukin-17
  • Interleukin-6
  • Immunoglobulin G