NLRP3 Disturbs Treg/Th17 Cell Balance to Aggravate Apical Periodontitis.

Abstract

Apical periodontitis is an inflammatory condition that is considered an immunological reaction of the periapical tissue to invading bacteria and their pathogenic components. Recent research has revealed that NLR family pyrin domain containing 3 (NLRP3) is crucial to the pathogenesis of apical periodontitis and serves as a link between innate and adaptive immunity. The balance between regulatory T-cell (Treg) and T helper cell 17 (Th17 cell) determines the direction of the inflammatory response. Therefore, this study aimed to investigate whether NLRP3 exacerbated periapical inflammation by disturbing Treg/Th17 balance and the underlying regulatory mechanisms. In the present study, NLRP3 was raised in apical periodontitis tissues as opposed to healthy pulp tissues. Low NLRP3 expression in dendritic cells (DCs) increased transforming growth factor β secretion while decreasing interleukin (IL)-1β and IL-6 production. The Treg ratio and IL-10 secretion rose when CD4+ T cells were cocultured with DCs primed with IL-1β neutralizing antibody (anti-IL-1β) and specific small interfering RNA (siRNA) targeting NLRP3 (siRNA NLRP3), but the proportion of Th17 cells and IL-17 release dropped. Furthermore, siRNA NLRP3-mediated suppression of NLRP3 expression aided Treg differentiation and elevated Foxp3 expression as well as IL-10 production in CD4+ T cells. Inhibition of NLRP3 activity by MCC950 boosted the percentage of Tregs while decreasing the ratio of Th17 cells, leading to reduced periapical inflammation and bone resorption. Nigericin administration, however, exacerbated periapical inflammation and bone destruction with an unbalanced Treg/Th17 response. These findings demonstrate that NLRP3 is a pivotal regulator by regulating the release of inflammatory cytokines from DCs or directly suppressing Foxp3 expression to disturb Treg/Th17 balance, thus exacerbating apical periodontitis.

• Authors: S Leng, W Xu, L Wu, L Liu, J Du, F Yang, D Huang, L Zhang
• Journal: Journal of dental research (J Dent Res) Vol. 102 Issue 6 Pg. 656-666 (06 2023) ISSN: 1544-0591 [Electronic] United States
• PMID: 36883625 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Forkhead Transcription Factors
• Interleukin-10
• NLR Family, Pyrin Domain-Containing 3 Protein
• RNA, Small Interfering
• NLRP3 protein, human

Topics

• Humans
• Forkhead Transcription Factors
• Inflammation
• Interleukin-10
• NLR Family, Pyrin Domain-Containing 3 Protein (metabolism)
• Periapical Periodontitis
• RNA, Small Interfering
• T-Lymphocytes, Regulatory
• Th17 Cells