Influence of Natural Killer Cells and Natural Killer T Cells on Periodontal Disease: A Systematic Review of the Current Literature

Abstract

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.

Keywords: adaptive immunity; host defense; innate immunity; natural killer T cells; natural killer cells; periodontitis.

Figure 1

Flow diagram containing the process of study selection.

Figure 2

Color code indicating mechanisms of natural killer (NK) cells and/or natural killer T (NKT) cells in periodontitis.

Figure 3

Proinflammatory properties of NK cells in periodontitis: The references and experimental study model are given in parentheses (human, animal, and in vitro). NK cell—natural killer cell; DC—dendritic cell; gF—gingival fibroblast; KIR—killer cell immunoglobulin-like receptor; CRACC—CD2-like receptor-activating cytotoxic cell; NCR-1—natural cytotoxicity triggering receptor 1; IL—interleukin; TLR—Toll-like receptor; MHC—major histocompatibility complex; TNF-α—tumor necrosis factor alpha; and CXCL—CXC-motif ligand chemokine.

Figure 4

Possible models of immunoregulatory properties and uncertain biological relevance of NK cells in periodontitis: The references and experimental study model are given in parentheses (human, animal, and in vitro). NK cell—natural killer cell; KIR—killer cell immunoglobulin-like receptor; CRACC, CD2-like receptor-activating cytotoxic cell; NCR-1—natural cytotoxicity triggering receptor 1; IgG—immunoglobulin G; and TLR—Toll-like receptor.

Figure 5

Possible models of NKT cell-mediated mechanisms in periodontitis: The references and experimental study model is given in parentheses (human, animal, and in vitro). NK—natural killer cell; NKT—natural killer T cell; DC—dendritic cell; iNKT cell—invariant natural killer T cell; TH—T helper cell; TCR—T-cell receptor; KIR—killer cell immunoglobulin-like receptor; CRACC—CD2-like receptor-activating cytotoxic cell; NCR-1—natural cytotoxicity triggering receptor 1; IL—interleukin; TLR—Toll-like receptor; and CD—cluster of differentiation.