Calcium Signaling in T Cells and Chronic Inflammatory Disorders of the Oral Cavity

Abstract

Acute immune responses to microbial insults in the oral cavity often progress to chronic inflammatory diseases such as periodontitis and apical periodontitis. Chronic oral inflammation causes destruction of the periodontium, potentially leading to loss of the dentition. Previous investigations have demonstrated that the composition of oral immune cells, rather than the overall extent of cellular infiltration, determines the pathological development of chronic inflammation. The role of T lymphocyte populations, including Th1, Th2, Th17, and Treg cells, has been extensively described. Studies now propose pathogenic Th17 cells as a distinct subset, uniquely classifiable from traditional Th17 populations. In situ differentiation of pathogenic Th17 cells has been verified as a source of destructive inflammation, which critically drives pathogenesis in chronic inflammatory diseases such as diabetes, rheumatoid arthritis, and inflammatory bowel disease. Pathogenic Th17 cells resemble a Th1 penotype and produce not only interleukin 17 (IL-17) but also γ-interferon (IFN-γ) and granulocyte-macrophage colony-stimulating factor (GM-CSF). The proinflammatory cytokine-specific mechanisms known to induce IL-17 expression in Th17 cells are well characterized; however, differentiation mechanisms that lead to pathogenic Th17 cells are less understood. Recently, Ca2+ signaling through Ca2+ release-activated Ca2+ channels (CRAC) in T cells has been uncovered as a major signaling axis involved in the regulation of T-cell-mediated chronic inflammation. In particular, pathogenic Th17 cell–mediated immunological diseases appear to be effectively targeted via such Ca2+ signaling pathways. Pathogenic plasticity of Th17 cells has been extensively illustrated in autoimmune and chronic inflammatory diseases. Although their specific causal relationship to oral infection-induced chronic inflammatory diseases is not fully established, pathogenic Th17 cells may be involved in the underlining mechanism. This review highlights the current understanding of T-cell phenotype regulation, calcium signaling pathways in this event, and the potential role of pathogenic Th17 cells in chronic inflammatory disorders of the oral cavity.

Mechanisms of bone remodeling and therapeutic strategies in chronic apical periodontitis

“…Th17 cells also stimulate the colony of neutrophils, triggering an inflammatory response to stimulate osteoclast activity, whereas neutrophil clearance of infection inhibits osteoclast activity (Wei et al, 2021). In addition, IL-1b, IL-6, IL-21, IL-23, and in periapical inflammatory environment can stimulate the upregulation of STAT3 and NFAT in Th17 cells, further increase the levels of IL-22, IL-21, IL-17F, IL-17A, and pathologically up-regulate the expressions of IFN-g and GM-CSF (Hasiakos et al, 2021).…”

Mechanism of bisphosphonate-related osteonecrosis of the jaw (BRONJ) revealed by targeted removal of legacy bisphosphonate from jawbone using competing inert hydroxymethylene diphosphonate

“…The fraction of T cells in the untreated BRONJ mice contained Cd8a +cytotoxic T cells and the upregulated expression of T cell costimulatory molecule CD27 ( Figure 6C ), suggesting the presence of mature CD4+ and CD8+ T cell function ( Hendriks et al, 2000 ). Furthermore, a small but distinct expression of Il17f indicated the differentiation of highly pro-inflammatory Th17 cells ( Hasiakos et al, 2021 ) in the BRONJ lesion. The oral barrier cells from HMDP-DNV treated mice did not show these proinflammatory signatures.…”

Network pharmacology combined with GEO database identifying the mechanisms and molecular targets of Polygoni Cuspidati Rhizoma on Peri-implants

“…As mentioned above, T cell signaling pathways are hypothesized to be key mediators of persistent infection-induced chronic inflammatory processes in periodontitis and periapical periodontitis which is also influenced by Ca 2+ signaling pathways and Ca 2+ channel regulation. With advances in the study of Ca 2+ signaling pathways in T cell pathogenicity and homeostasis, oral barrier immune cells may be affected by CCB and may lead to inflammatory gingival enlargement 55 . As you can imagine, the susceptibility of periodontitis or Peri-implants are directly related to calcium signaling or dysfunction.…”