The Role of Dendritic Cells during Physiological and Pathological Dentinogenesis

Quispe-Salcedo, Ángela; Ohshima, Hayato

doi:10.3390/jcm10153348

Cited by 5 publications

(4 citation statements)

References 116 publications

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“…The M2 phenotype macrophages co-localize with Schwann cells in the human dental pulp and play a role in promoting odontogenic differentiation of human dental pulp cells ( Park et al, 2017 ; Yoshiba et al, 2020 ). The large proportion of dendritic cells in Y1 MPs ( Supplementary Figure S1B ) is consistent with previous studies describing their possible role in dentin formation ( Quispe-Salcedo and Ohshima, 2021 ). The interaction of OSM/OSMR between MPs and ECs in Y1 could be related to its role in the early sample ( Figure 2E ).…”

Section: Discussionsupporting

confidence: 91%

Atlas of human dental pulp cells at multiple spatial and temporal levels based on single-cell sequencing analysis

Ren¹,

Wen

Zhao³

et al. 2022

Front. Physiol.

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The dental pulp plays a crucial role in the long-term maintenance of tooth function. The progress of endodontic treatment and pulp tissue regeneration engineering has made pulp-regeneration therapy promising in clinical practice. However, the mechanisms of pulp regeneration and the role of dental stem cells in development and regeneration have not been fully elucidated. Bridging the gaps between clinical operation and basic research is urgently needed. With the application of single-cell sequencing technology in dental research, the landscapes of human dental pulp cells have begun being outlined. However, the specific cellular heterogeneity of dental pulp cells, especially that of dental stem cells, at different spatial and temporal levels, is still unclear. In this study, we used single-cell RNA sequencing analysis of pulp samples at four different developmental stages and combined the findings with immunohistochemical staining to explore the development of dental pulp and stem cells. The results revealed temporal changes in the proportion of pulp cells during development. For example, mononuclear phagocytes accounted for a higher proportion in early samples. Odontoblasts identified by DMP1 had a higher expression of ion channel-related and neurodevelopment-related genes. Subpopulations were identified in fibroblasts, odontoblasts, and mesenchymal stem cells. We identified a subclass of odontoblasts that expresses DGKI and RRBP1 present in early developmental samples. A population of earlier mesenchymal stem cells expressed the SEPTIN gene, which may have greater proliferative and differentiation potential. Furthermore, dental pulp stem cells can differentiate into two directions: mineralization and myogenesis. In summary, the specific cellular heterogeneity of dental pulp cells was revealed at different spatial and temporal levels. These findings may shed light on the mechanism of tooth development. The gene expression profile of developing pulp cells may help to select cells for regenerative engineering and improve the success of dental pulp regeneration.

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Section: Discussionsupporting

confidence: 91%

Atlas of human dental pulp cells at multiple spatial and temporal levels based on single-cell sequencing analysis

Ren¹,

Wen

Zhao³

et al. 2022

Front. Physiol.

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“…Quispe‐Salcedo and Ohshima (2021) concluded the role of DCs in different processes of odontogenesis where they actively interact with fronter odontoblasts adjacent to the peri‐vessels in the odontoblasts layer, contributing to odontogenic development and responding external stimuli. The expression of CD83 represents the maturation of antigen‐presenting cells, typically DCs, and activation of T cells (Li et al., 2019).…”

Section: Discussionmentioning

confidence: 99%

“…Dental pulp owns an integral immune defence system against infection. The term “dentine‐pulp complex immunology”, involving immune cells, dental pulp cells and odontoblasts, reflects a trend in the research of dental pulp immunobiology (Quispe‐Salcedo & Ohshima, 2021). Transcriptomics algorithms predicting immune cell abundance have been undergoing continual development and make it easier to explore the immune landscape of dental pulp.…”

Section: Introductionmentioning

confidence: 99%

Osteopontin interacts with dendritic cells and macrophages in pulp inflammation: Comprehensive transcriptomic analysis and laboratory investigations

Chen,

Zhu,

Zhang

et al. 2024

Int Endodontic J

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AimTo investigate novel diagnostic markers for pulpitis and validate by clinical samples from normal and inflamed pulp. To explore the relationship between diagnostic markers and immune cells or their phenotypes during pulp inflammation.MethodologyTwo microarray datasets, GSE77459 and GSE92681, and identified differential expression genes were integrated. To understand immune features, gene functions, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Disease Ontology (DO) and ImmuneSigDB Gene Set Enrichment Analysis (GSEA) were analysed. For predictive purposes, machine learning techniques were applied to detect diagnostic markers. Immune infiltration in inflamed pulp was studied using CIBERSORT. The relationship between diagnostic markers and immune cells was investigated and validated their gene expression in clinical samples from the normal or inflamed pulp by qRT‐PCR. Finally, the correlation between one marker, secreted phosphoprotein 1 (SPP1), encoding osteopontin (OPN), and dendritic cells (DCs)/macrophages was identified via HE staining and multiplex immunohistochemistry. An in vitro inflammatory dental pulp microenvironment model of THP‐1 macrophages cocultured with dental pulp cells derived conditioned media (DPCs‐CM) to investigate OPN production and macrophage phenotypes was established.ResultsAnalysis revealed unique immunologic features in inflamed pulp. Three diagnostic markers for pulpitis: endothelin‐1 (EDN1), SPP1, and purine nucleoside phosphorylase (PNP), and validated them using qRT‐PCR were predicted. Multiplex immunohistochemistry demonstrated OPN co‐localized with activated DCs and M2 macrophages during pulp inflammation. In vitro experiments showed that THP‐1 macrophages produced the highest levels of OPN when stimulated with DPCs‐CM derived from the 20 μg/mL LPS pre‐conditioned group, suggesting an M2b‐like phenotype by increasing surface marker CD86 and expression of IL6, TNFα, IL10, and CCL1 but not CCL17 and MerTK. Levels of CCL1 and IL10 elevated significantly in the macrophages' supernatant from the 20 μg/mL LPS pre‐conditioned CM group. OPN was proven co‐localizing with CD86 in the inflamed pulp by immunofluorescence.ConclusionsThe current findings suggest that OPN can serve as a promising biomarker for pulpitis, correlated with DCs and macrophages. OPN+ macrophages in the inflamed pulp are associated with M2b‐like phenotypes. These insights offer the potential for improved diagnosis and targeted therapy.

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“…These CD11c+ dendritic cells can migrate to the draining lymph nodes for antigen processing and presentation at the later stage of the immune response [ 14 ]. Reportedly, in rat and human teeth, the expression of putative dendritic cell markers was observed in several cells extending cytoplasmic processes into dentinal tubules at the dentin-pulp interface [ 19 , 41 , 42 ]. These cells also increased at the early time points in the pathological condition, suggesting their involvement in the initial defense role in the pulpal immune response.…”

Section: Discussionmentioning

confidence: 99%

3D Visualization of Dynamic Cellular Reaction of Pulpal CD11c+ Dendritic Cells against Pulpitis in Whole Murine Tooth

Hong

Park

Lee

et al. 2021

IJMS

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In dental pulp, diverse types of cells mediate the dental pulp immunity in a highly complex and dynamic manner. Yet, 3D spatiotemporal changes of various pulpal immune cells dynamically reacting against foreign pathogens during immune response have not been well characterized. It is partly due to the technical difficulty in detailed 3D comprehensive cellular-level observation of dental pulp in whole intact tooth beyond the conventional histological analysis using thin tooth slices. In this work, we validated the optical clearing technique based on modified Murray’s clear as a valuable tool for a comprehensive cellular-level analysis of dental pulp. Utilizing the optical clearing, we successfully achieved a 3D visualization of CD11c+ dendritic cells in the dentin-pulp complex of a whole intact murine tooth. Notably, a small population of unique CD11c+ dendritic cells extending long cytoplasmic processes into the dentinal tubule while located at the dentin-pulp interface like odontoblasts were clearly visualized. 3D visualization of whole murine tooth enabled a reliable observation of these rarely existing cells with a total number less than a couple of tens in one tooth. These CD11c+ dendritic cells with processes in the dentinal tubule were significantly increased in the dental pulpitis model induced by mechanical and chemical irritation. Additionally, the 3D visualization revealed a distinct spatial 3D arrangement of pulpal CD11c+ cells in the pulp into a front-line barrier-like formation in the pulp within 12 h after the irritation. Collectively, these observations demonstrated the unique capability of optical clearing-based comprehensive 3D cellular-level visualization of the whole tooth as an efficient method to analyze 3D spatiotemporal changes of various pulpal cells in normal and pathological conditions.

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The Role of Dendritic Cells during Physiological and Pathological Dentinogenesis

Cited by 5 publications

References 116 publications

Atlas of human dental pulp cells at multiple spatial and temporal levels based on single-cell sequencing analysis

Atlas of human dental pulp cells at multiple spatial and temporal levels based on single-cell sequencing analysis

Osteopontin interacts with dendritic cells and macrophages in pulp inflammation: Comprehensive transcriptomic analysis and laboratory investigations

3D Visualization of Dynamic Cellular Reaction of Pulpal CD11c+ Dendritic Cells against Pulpitis in Whole Murine Tooth

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