Telocytes regulate macrophages in periodontal disease
- King's College London, United Kingdom
Abstract
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 including the heart1, lung2 and intestine3, their tissue-specific roles are poorly understood. Here we identify a specific cell signalling role for telocytes in the periodontium whereby telocytes regulate macrophage activity. We performed scRNA-seq and lineage tracing to identify telocytes and macrophages in mouse periodontium in homeostasis and periodontitis and carried out HGF signalling inhibition experiments using Tivantinib. We show that telocytes 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 state. Our results reveal the source of HGF signals in periodontal tissue and provide new insights into the function of telocytes in regulating macrophage behaviour in periodontitis through HGF/Met cell signalling, that may provide a novel approach in periodontitis treatment.
Data availability
Sequencing data have been deposited in GEO under accession codes GSE167917 and GSE160358.
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Telocytes regulate tissue resident macrophages in periodontal diseaseNCBI Gene Expression Omnibus, GSE167917.
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Periodontal ligament tissue periodontitisNCBI Gene Expression Omnibus, GSM5115470.
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Cells in healthy periodontal ligamentNCBI Gene Expression Omnibus, GSE160358.
Article and author information
Author details
Funding
Chinese Academy of Agricultural Sciences (N/A)
- Paul Sharpe
NIHR BioResource (N/A)
- Paul Sharpe
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Bérénice A Benayoun, University of Southern California, United States
Ethics
Animal experimentation: All mouse work was approved by UK Home Office under the project license 70/7866 and P5F0A1579, approved by the KCL animal ethics committee.
Version history
- Preprint posted: June 3, 2021 (view preprint)
- Received: July 12, 2021
- Accepted: September 26, 2022
- Accepted Manuscript published: October 4, 2022 (version 1)
- Accepted Manuscript updated: October 10, 2022 (version 2)
- Version of Record published: October 17, 2022 (version 3)
Copyright
© 2022, Zhao et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Telocytes regulate macrophages in periodontal disease
eLife 11:e72128.
https://doi.org/10.7554/eLife.72128
Further reading
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Asymmetric cell divisions (ACDs) generate two daughter cells with identical genetic information but distinct cell fates through epigenetic mechanisms. However, the process of partitioning different epigenetic information into daughter cells remains unclear. Here, we demonstrate that the nucleosome remodeling and deacetylase (NuRD) complex is asymmetrically segregated into the surviving daughter cell rather than the apoptotic one during ACDs in Caenorhabditis elegans. The absence of NuRD triggers apoptosis via the EGL-1-CED-9-CED-4-CED-3 pathway, while an ectopic gain of NuRD enables apoptotic daughter cells to survive. We identify the vacuolar H+–adenosine triphosphatase (V-ATPase) complex as a crucial regulator of NuRD’s asymmetric segregation. V-ATPase interacts with NuRD and is asymmetrically segregated into the surviving daughter cell. Inhibition of V-ATPase disrupts cytosolic pH asymmetry and NuRD asymmetry. We suggest that asymmetric segregation of V-ATPase may cause distinct acidification levels in the two daughter cells, enabling asymmetric epigenetic inheritance that specifies their respective life-versus-death fates.
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