Telocytes regulate macrophages in periodontal disease

Abstract

BackgroundTelocytes (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 heart1, lung2 and intestine3, their tissue-specific roles are poorly understood. Here we identify a cell signalling role for telocytes in the periodontium whereby telocytes regulate macrophage activity. MethodsWe 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. ResultsWe 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. ConclusionsOur 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 O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=114 SRC="FIGDIR/small/446871v2_ufig1.gif" ALT="Figure 1"> View larger version (18K): org.highwire.dtl.DTLVardef@12e0491org.highwire.dtl.DTLVardef@2de4d0org.highwire.dtl.DTLVardef@10936a8org.highwire.dtl.DTLVardef@1e36089_HPS_FORMAT_FIGEXP M_FIG 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. C_FIG