Identification of the characteristics of infiltrating immune cells in pulpitis and its potential molecular regulation mechanism by bioinformatics method

Abstract

Objective The inflammation of dental pulp will also trigger an immune response. The purpose of this study is to demonstrate the immune cell’s function and explore their regulatory molecules and signal pathways in pulpitis. Method The CIBERSORTx method was used to quantitatively analyze 22 types of immune cells infiltrating in the GSE77459 dataset of dental pulp tissues. The immune-related differential genes (IR-DEGs) were further screened and enriched for the GO and KEGG pathways. Protein–protein interaction (PPI) networks were constructed and the hub IR-DEGs were screened. Finally, we constructed the regulatory network of hub genes. Results The GSE77459 dataset screened 166 IR-DEGs and was enriched for three signal pathways involved in pulpitis development: chemokine signaling, TNF signaling, and NF-κB signaling. Significant differences in immune cell infiltration were observed between normal and inflamed dental pulp. The proportions of M0 macrophages, neutrophils, and follicular helper T cells were significantly higher than that of the normal dental pulp, while the proportions of resting mast cells, resting dendritic cells, CD8 T cells, and monocytes were significantly lower. The random forest algorithm concluded that M0 macrophages and neutrophils were the two most important immune cells. We identified five immune-related hub genes IL-6, TNF-α, IL-1β, CXCL8, and CCL2. In addition, IL-6, IL-1β, and CXCL8 are highly correlated with M0 macrophages and neutrophils, and the five hub genes have many shared regulatory molecules: four miRNAs and two lncRNAs, three transcription factors. Conclusion Immune cell infiltration plays an important role in pulpitis among which M0 macrophages and neutrophils are the most significant immune cells. IL-6, TNF-α, IL-1, CXCL8, and CCL2 may be essential molecule of the immune response regulation network in pulpitis. This will help us understand the immune regulatory network in pulpitis.

Expression of Toll-like Receptors in Stem Cells of the Apical Papilla and Its Implication for Regenerative Endodontics

“…Microbial infections trigger a robust immunological response in the dental pulp [4,5]. The recognition of pathogen-associated molecular patterns (PAMPs) in dental infections 2 of 12 by pathogen pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs), represents one of the first steps in the defense response.…”

Chemokine‑like receptor 1‑positive cells are present in the odontoblast layer in tooth tissue in rats and humans

“…A number of studies have investigated inflammation of the dental pulp (7)(8)(9)(10); however, further clarification of the mechanism of pulp inflammation is expected to lead to more reliable treatment of pulpitis. Suppression of pulpal inflammation and induction of remineralization have also been investigated (7,(11)(12)(13) and are considered to be important in dental treatment to preserve the dental pulp or to regenerate the tooth structure (14)(15)(16).…”