Th17-to-Tfh plasticity during periodontitis limits disease pathology.

MCCLURE, Flora A, WEMYSS, Kelly, COX, Joshua R, BRIDGEMAN, Hayley M, PRISE, Ian E, KING, James I, JAIGIRDAR, Shafqat, WHELAN, Annie, JONES, Gareth W, GRAINGER, John R, HEPWORTH, Matthew R and KONKEL, Joanne E (2024). Th17-to-Tfh plasticity during periodontitis limits disease pathology. The Journal of experimental medicine, 221 (8): e20232015.

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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.

Item Type:	Article
Uncontrolled Keywords:	Gingiva; Animals; Mice, Inbred C57BL; Mice; Alveolar Bone Loss; Periodontitis; Immunoglobulin G; Interleukin-6; Interleukin-17; Th17 Cells; Cell Plasticity; T Follicular Helper Cells; Th17 Cells; Animals; Periodontitis; Cell Plasticity; Interleukin-17; Mice; Interleukin-6; Mice, Inbred C57BL; T Follicular Helper Cells; Gingiva; Immunoglobulin G; Alveolar Bone Loss; 11 Medical and Health Sciences; Immunology; 32 Biomedical and clinical sciences; 42 Health sciences
Identification Number:	https://doi.org/10.1084/jem.20232015
SWORD Depositor:	Symplectic Elements
Depositing User:	Symplectic Elements
Date Deposited:	13 Jun 2024 16:18
Last Modified:	13 Jun 2024 16:30
URI:	https://shura.shu.ac.uk/id/eprint/33833

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