The dental pulp is an immunologically active tissue that responds dynamically to cariogenic challenge. Peripheral pulp cells adjacent to dentine encounter bacterial stimuli earlier than cells located Show more
The dental pulp is an immunologically active tissue that responds dynamically to cariogenic challenge. Peripheral pulp cells adjacent to dentine encounter bacterial stimuli earlier than cells located in the central pulp. To investigate signalling and immune interactions, this study profiled the transcriptomes of dentine-adherent cells (DACs) and central dental pulp cells (DPCs) cocultured with Streptococcus mutans. Primary cultures of both DACs and DPCs were obtained from healthy third molars of three female and three male donors aged 13-16. Cells were cocultured with viable S. mutans (2 × 10 RNA-Seq revealed a dynamic shift in the transcriptome of DACs and DPCs stimulated with S. mutans, while cells exposed to γ-inactivated or no bacteria did not. Although DACs and DPCs shared common DEGs (33 up, 8 down), several regulations were exclusive to DACs (22 up, 9 down) and DPCs (9 up, 25 down), highlighting a donor-independent functional specificity of the pulp subpopulations. Functional enrichment analysis revealed a strong and comparable activation of hypoxia-related pathways in both DPCs and DACs. However, DACs additionally showed enrichment in extracellular matrix organisation and cytokine signalling, while DPCs were characterised by intracellular stress responses and protein folding pathways. Additionally, protein-protein interaction analysis identified IL-6 as a key hub in DACs, while ANGPTL4 was central in DPCs. Following exposure to S. mutans, mechanically isolated DACs and DPCs displayed distinct transcriptomic profiles, indicating functional heterogeneity in the pulpal immune response. DACs engaged immunomodulatory pathways, while DPCs were marked by cellular stress responses, suggesting divergent contributions to tissue defence and homeostasis. Show less
Most of the current therapies, as well as many of the clinical trials, for multiple sclerosis (MS) target the inflammatory autoimmune processes, but less than 20% of all clinical trials investigate po Show more
Most of the current therapies, as well as many of the clinical trials, for multiple sclerosis (MS) target the inflammatory autoimmune processes, but less than 20% of all clinical trials investigate potential therapies for the chronic progressive disease stage of MS. The latter is responsible for the steadily increasing disability in many patients, and there is an urgent need for novel therapies that protect nervous system tissue and enhance axonal growth and/or remyelination. As outlined in this review, solid pre-clinical data suggest neutralization of the neurite outgrowth inhibitor Nogo-A as a potential new way to achieve both axonal and myelin repair. Several phase I clinical studies with anti-Nogo-A antibodies have been conducted in different disease paradigms including MS and spinal cord injury. Data from spinal cord injury and amyotrophic lateral sclerosis (ALS) trials accredit a good safety profile of high doses of anti-Nogo-A antibodies administered intravenously or intrathecally. An antibody against a Nogo receptor subunit, leucine rich repeat and immunoglobulin-like domain-containing protein 1 (LINGO-1), was recently shown to improve outcome in patients with acute optic neuritis in a phase II study. Nogo-A-suppressing antibodies could be novel drug candidates for the relapsing as well as the progressive MS disease stage. In this review, we summarize the available pre-clinical and clinical evidence on Nogo-A and elucidate the potential of Nogo-A-antibodies as a therapy for progressive MS. Show less