Natural killer (NK) cells, as members of the innate immune system, and natural killer T (NKT) cells, bridging innate and adaptive immunity, play a prominent role in chronic inflammatory diseases and cancerogenesis, yet have scarcely been examined in oral diseases. Therefore, systematic research on the latest literature focusing on NK/NKT cell-mediated mechanisms in periodontal disease, including the time period 1988–2020, was carried out in MEDLINE (PubMed) using a predetermined search strategy, with a final selection of 25 studies. The results showed that NK cells tend to have rather proinflammatory influences via cytokine production, cytotoxic effects, dendritic-cell-crosstalk, and autoimmune reactions, while contrarily, NKT cell-mediated mechanisms were proinflammatory and immunoregulatory, ranging from protective effects via B-cell-regulation, specific antibody production, and the suppression of autoimmunity to destructive effects via cytokine production, dendritic-cell-crosstalk, and T-/B-cell interactions. Since NK cells seem to have a proinflammatory role in periodontitis, further research should focus on the proinflammatory and immunoregulatory properties of NKT cells in order to create, in addition to antibacterial strategies in dental inflammatory disease, novel anti-inflammatory therapeutic approaches modulating host immunity towards dental health.

The human oral microbiota consists of over 700 widespread taxa colonizing the oral cavity in several anatomically diverse oral niches. Lately, sequencing of the 16S rRNA genes has become an acknowledged, culture-independent method to characterize the oral microbiota. However, only a small amount of data are available concerning microbial differences between oral niches in periodontal health and disease. In the context of periodontitis, the cytokine expression in the gingival crevicular fluid has been studied in detail, whereas little is known about the cytokine profile in hard and soft tissue biofilms. In order to characterize oral niches in periodontal health, the oral microbiota and cytokine pattern were analyzed at seven different sites (plaque (P), gingival crevicular fluid (GCF), saliva (S), tongue (T), hard palate (HP), cheek (C) and sublingual area (U)) of 20 young adults using next-generation sequencing and multiplex immunoassays. Site-specific microbial compositions were detected, which clustered into three distinct metaniches (“P-GCF”, “S-T-HP” and “C-U”) and were associated with niche-/metaniche-specific cytokine profiles. Our findings allow the definition of distinct metaniches according to their microbial composition, partly reflected by their cytokine profile, and provide new insights into microenvironmental similarities between anatomical diverse oral niches.

The periodontal ligament (PDL) is exposed to different kinds of mechanical stresses such as bite force or orthodontic tooth movement. A simple and efficient model to study molecular responses to mechanical stress is the application of compressive force onto primary human periodontal ligament fibroblasts via glass disks. Yet, this model suffers from the need for primary cells from human donors which have a limited proliferative capacity. Here we show that an immortalized cell line, PDL-hTERT, derived from primary human periodontal ligament fibroblasts exhibits characteristic responses to glass disk-mediated compressive force resembling those of primary cells. These responses include induction and secretion of pro-inflammatory markers, changes in expression of extracellular matrix-reorganizing genes and induction of genes related to angiogenesis, osteoblastogenesis and osteoclastogenesis. The fact that PDL-hTERT cells can easily be transfected broadens their usefulness, as molecular gain- and loss-of-function studies become feasible.

The transcription factor Sox10 is an essential regulator of genes that code for structural components of the myelin sheath and for lipid metabolic enzymes in both types of myelinating glia in the central and peripheral nervous systems. In an attempt to characterize additional Sox10 target genes in Schwann cells, we identified in this study a strong influence of Sox10 on the expression of genes associated with adhesion in the MSC80 Schwann cell line. These included the genes for Gliomedin, Neuronal cell adhesion molecule and Neurofascin that together constitute essential Schwann cell contributions to paranode and node of Ranvier. Using bioinformatics and molecular biology techniques we provide evidence that Sox10 directly activates these genes by binding to conserved regulatory regions. For activation, Sox10 cooperates with Krox20, a transcription factor previously identified as the central regulator of Schwann cell myelination. Both the activating function of Sox10 as well as its cooperation with Krox20 were confirmed in vivo. We conclude that the employment of Sox10 and Krox20 as regulators of structural myelin sheath components and genes associated with the node of Ranvier is one way of ensuring a biologically meaningful coordinated formation of both structures during peripheral myelination.

Oligodendroglial cells generate myelin sheaths in the vertebrate central nervous system to render rapid saltatory conduction possible and express the highly related Sox8, Sox9 and Sox10 transcription factors. While Sox9 and Sox10 fulfill crucial regulatory roles, Sox8 has only a limited impact on oligodendroglial development and myelination. By replacing Sox10 with Sox8 or Sox9 in the oligodendroglial Oln93 cell line, and comparing the expression profiles, we show here that Sox8 regulates the same processes as Sox10 and Sox9, but exhibits a substantially lower transcriptional activity under standard culture conditions. Sox8 influences fewer genes in their expression and changes their expression level less drastically, despite comparable binding to relevant regulatory regions in oligodendroglial cells. Therefore, it is likely that Sox8 and Sox10 vary in their transcriptional activity because of differences in their interactions with partner proteins. Intriguingly, it is the aminoterminal one third of the Sox protein that is responsible for the differential activities of Sox8 and Sox10, rather than the carboxyterminal two thirds that contain the known transactivation domains. Our study aims to provide an understanding of the relationship of Sox8 and Sox10 as paralogous transcription factors and their degree of functional redundancy in oligodendroglial cells, along with implications for health and disease.

The diagnosis of an ectodermal dysplasia (ED) is often made by dermatologists. Some of the more than 50 distinct ectodermal dysplasias, however, are still largely unknown and their pathogenesis is poorly understood. Since we recently discovered that variants of the Interferon Regulatory Factor 6 (IRF6) gene IRF6 may cause ED, we have further investigated the link between this gene and maldevelopment of tissues originating from the embryonic ectoderm. Disease characterization in two previously reported subjects and one newly identified patient (mosaic status) included systematic clinical and genetic evaluation, assessment of all available patient records and dental radiographs, hearing tests and immunostaining of skin samples. Structural models of native and mutant IRF6 were analysed to elucidate the pathogenesis. IRF6‐associated ED, a combination of natal teeth (irregularly), absent sweat glands, hidradenitis suppurativa‐like symptoms, onychodysplasia, agenesis of numerous deciduous and permanent teeth, and sensorineural hearing impairment, was linked to amino acid substitutions in a region between the DNA‐binding domain and the protein‐binding domain of IRF6, which has not yet been assigned a function. Genotype–phenotype correlations from a total of five patients and immunohistochemical data support the assumption that IRF6‐associated ED is based on a gain‐of‐function mechanism. Thus, IRF6 variants are not only the cause of Van der Woude syndrome and popliteal pterygium syndrome, two diseases with cleft lip/palate as common features, but are most likely responsible also for a new, challenging syndrome without orofacial clefting. Our results facilitate accurate and early diagnosis in affected individuals and may pave the way for specific treatment.