Mast Cell Cytokines in Acute and Chronic Gingival Tissue Inflammation: Role of IL-33 and IL-37

Abstract

Much evidence suggests autoimmunity in the etiopathogenesis of periodontal disease. In fact, in periodontitis, there is antibody production against collagen, DNA, and IgG, as well as increased IgA expression, T cell dysfunction, high expression of class II MHC molecules on the surface of gingival epithelial cells in inflamed tissues, activation of NK cells, and the generation of antibodies against the azurophil granules of polymorphonuclear leukocytes. In general, direct activation of autoreactive immune cells and production of TNF can activate neutrophils to release pro-inflammatory enzymes with tissue damage in the gingiva. Gingival inflammation and, in the most serious cases, periodontitis, are mainly due to the dysbiosis of the commensal oral microbiota that triggers the immune system. This inflammatory pathological state can affect the periodontal ligament, bone, and the entire gingival tissue. Oral tolerance can be abrogated by some cytokines produced by epithelial cells and activated immune cells, including mast cells (MCs). Periodontal cells and inflammatory–immune cells, including mast cells (MCs), produce cytokines and chemokines, mediating local inflammation of the gingival, along with destruction of the periodontal ligament and alveolar bone. Immune-cell activation and recruitment can be induced by inflammatory cytokines, such as IL-1, TNF, IL-33, and bacterial products, including lipopolysaccharide (LPS). IL-1 and IL-33 are pleiotropic cytokines from members of the IL-1 family, which mediate inflammation of MCs and contribute to many key features of periodontitis and other inflammatory disorders. IL-33 activates several immune cells, including lymphocytes, Th2 cells, and MCs in both innate and acquired immunological diseases. The classic therapies for periodontitis include non-surgical periodontal treatment, surgery, antibiotics, anti-inflammatory drugs, and surgery, which have been only partially effective. Recently, a natural cytokine, IL-37, a member of the IL-1 family and a suppressor of IL-1b, has received considerable attention for the treatment of inflammatory diseases. In this article, we report that IL-37 may be an important and effective therapeutic cytokine that may inhibit periodontal inflammation. The purpose of this paper is to study the relationship between MCs, IL-1, IL-33, and IL-37 inhibition in acute and chronic inflamed gingival tissue.

Microbiota and IL-33/31 Axis Linkage: Implications and Therapeutic Perspectives in Atopic Dermatitis and Psoriasis

“…Nevertheless, the causal relationship between dysbiosis and AD or psoriasis remains unclear, and the molecular mechanisms by which changes in the microbiome lead to a chronic inflammatory response (or vice versa) in these diseases are still being investigated [40,71,72]. IL-33 has already been found to drive multiple scenarios of dysbiosis-associated chronic inflammation, including gastrointestinal [73,74], dental [75][76][77], allergologic [78][79][80], pulmonary [81] and oncologic [82] conditions, and a previous study by Murdaca et al reviewed the role of the IL-33/IL-31 axis in the development of autoimmune and allergic disorders, including AD [29].…”

Single‐cell sequencing, spatial transcriptome ad periodontitis: Rethink pathogenesis and classification

“…Several types of cells including fibroblasts, endothelial cells, immune cells, epithelial cells and undifferentiated mesenchymal cells orchestrate a dynamic response to fight bacterial invasion and reestablish a healthy status (Donos, 2018; Moutsopoulos & Konkel, 2018; Nunez et al, 2019; Saliem et al, 2022). Also, highly expressed inflammatory genes induce cytokine release in the environment as a defence mechanism to recruit cells (Pan et al, 2019; Trimarchi et al, 2022). However, no specific cells or gene drivers so far are linked exclusively to periodontal diseases.…”