Th17-to-Tfh plasticity during periodontitis limits disease pathology

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.