Investigating innate immune mechanisms in dentine-pulp complex repair

Abstract

Multiple studies are investigating how to modulate inflammation towards a reparative outcome, in the dental pulp in particular a recent study have found that odontoblast cell death in sterile inflammatory conditions leads to dental pulp cells (DPCs) proliferation, migration, and differentiation in an NLRP3 inflammasome-dependent manner. We hypothesised that inflammasome activity modulates caries-induced pulp inflammation and dentine repair.

To assess the effects of inflammatory stimuli on the reparative mechanisms of DPCs, the cells were exposed to lipopolysaccharide (LPS), lipoteichoic acid (LTA), or DNA (poly dA:dT). Among these, only DNA exposure inhibited all reparative functions of DPCs, including proliferation, migration, and mineralisation. This inhibitory effect was reversed when DNA sensors (TLR9, AIM2, and cGAS) were blocked using the A151 molecule. However, inhibition of inflammasome activity via caspase-1 did not affect this DNA-induced suppression.

In addition, this study highlights the critical role of immune cell recruitment in dental pulp repair. Using a co-culture model comprising DPCs and macrophages, we observed enhanced mineralisation capacity in DPCs following co-culture with unstimulated macrophages. This finding underscores the importance of an initial inflammatory response that facilitates immune cell recruitment to the site of injury, thereby promoting dentine production and tissue regeneration. While secretions of DNA-activated macrophages did not have an effect on DPCs reparative capacity.

In conclusion, this thesis demonstrates that DNA inhibits the reparative capacity of DPCs through an inflammasome-independent mechanism. Furthermore, it identifies the A151 inhibitor as a potential therapeutic agent that could be incorporated into dental materials to reverse DNA-induced suppression of repair.

Thesis is embargoed until 31 July 2031.

Date of Award	Jul 2026
Original language	English
Awarding Institution	Queen's University Belfast
Sponsors	Zarqa University
Supervisor	Yvonne Dombrowski (Supervisor), Ikhlas El Karim (Supervisor) & Fionnuala Lundy (Supervisor)