Th17-to-Tfh plasticity during periodontitis limits disease pathology

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

Research output: Contribution to journalArticlepeer-review

Abstract

In autoinflammatory diseases Th17 cell plasticity has been shown to be crucial for development of disease pathology. Periodontitis is a prevalent inflammatory disease where Th17 cells mediate key pathological roles, yet whether they exhibit any functional diversification that contributes to pathology during periodontitis remains unexplored. Using an IL-17A fate reporter mouse 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 lymph node draining the inflammatory site. Here some Th17 cells took on features of Tfh cells, a functional plasticity that was dependent on IL-6. Notably, we show that this Th17-to-Tfh diversification was important to limit periodontitis pathology. Preventing Th17-to-Tfh plasticity resulted in elevated periodontal bone loss which was not simply a result of 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
JournalJournal of Experimental Medicine
Publication statusAccepted/In press - 7 May 2024

Fingerprint

Dive into the research topics of 'Th17-to-Tfh plasticity during periodontitis limits disease pathology'. Together they form a unique fingerprint.

Cite this