Telocytes regulate macrophages in periodontal disease

Background: Telocytes (TCs) or interstitial cells are characterised in vivo by their long projections that contact other cell types. Although telocytes can be found in many different tissues in luding the heart, lung and intestine, their tissue-specific roles are poorly understood. Here we identify a cell signalling role for telocytes in the periodontium whereby telocytes regulate macrophage activity. Methods: We performed scRNA-seq and lineage tracing to identify TCs in mouse periodontium in homeostasis and periodontitis and carried out HGF signalling inhibition experiments using Tivantinib. Results: We demonstrated that TCs are quiescent in homeostasis, however, they proliferate and serve as a major source of HGF in periodontitis. Macrophages receive telocyte-derived HGF signals and shift from an M1 to a M1/M2 hybrid state. Conclusions: Our results reveal the source of HGF signals in periodontal tissue and provide new insights into the function of TCs in regulating macrophage behaviour in periodontitis through HGF/c-Met cell signalling, that may provide a novel approach in periodontitis treatment.