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 1 , lung 2 and intestine 3 , 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. Graphic abstract A population of telocytes (TC) have been identified in the periodontium. They are quiescent in homeostasis, however, in periodontitis, they are activated and send HGF signals to LPS activated iNOS+ (M1) macrophages. Macrophages receive the HGF signals via c-Met, which results in the expression of M2 marker Arg1, representing in an increase of M1/M2 hybrid macrophages. The expression of Arg1 can be inhibited by a HGF/c-Met selective inhibitor Tivantinib.