NLRP3 Disturbs Treg/Th17 Cell Balance to Aggravate Apical Periodontitis

Area of Science:

• Immunology
• Oral Biology
• Inflammation Research

Background:

• Apical periodontitis is an inflammatory disease driven by bacterial components.
• NLR family pyrin domain containing 3 (NLRP3) is implicated in apical periodontitis pathogenesis.
• The balance between regulatory T-cells (Tregs) and T helper 17 (Th17) cells dictates inflammatory responses.

Purpose of the Study:

• To investigate if NLRP3 exacerbates periapical inflammation by disrupting Treg/Th17 balance.
• To elucidate the underlying regulatory mechanisms of NLRP3 in this process.

Main Methods:

• Assessed NLRP3 expression in human apical periodontitis tissues.
• Utilized dendritic cells (DCs) and CD4+ T cells in co-culture experiments.
• Employed small interfering RNA (siRNA) targeting NLRP3 and NLRP3 inhibitor MCC950.
• Administered nigericin to induce inflammation.

Main Results:

• NLRP3 expression was elevated in apical periodontitis tissues.
• NLRP3 inhibition increased Treg differentiation and IL-10 production while decreasing Th17 cells and IL-17.
• MCC950 treatment reduced periapical inflammation and bone resorption.
• Nigericin exacerbated inflammation and bone destruction.

Conclusions:

• NLRP3 plays a pivotal role in apical periodontitis by disrupting Treg/Th17 balance.
• NLRP3 regulates inflammatory cytokine release from DCs and directly suppresses Foxp3 expression.
• Targeting NLRP3 may offer a therapeutic strategy for apical periodontitis.