Interleukin-17A-Producing Gamma Delta T Cells Accelerate Mineralization in Human Dental Pulp Stem Cells

γδ T cells, which express the T cell receptor γδ, contribute to both innate and adaptive immune responses, yet their role in dental pulp pathology remains poorly understood. This study investigated the impact of γδ T cells on the calcification of human dental pulp stem cells (HDPSCs) through interleukin-17A (IL-17A) signaling. Dental pulp tissues and peripheral blood mononuclear cells (PBMCs) were analyzed to detect the presence of γδ T cells using immunofluorescence and flow cytometry. γδ T cells were efficiently generated from PBMCs with IL-2 and zoledronate stimulation, producing IL-17A as confirmed by ELISA. In healthy pulp, γδ T cells constituted the predominant CD3-positive T cell population. Their presence increased significantly in inflamed pulp tissues, with IL-17A-expressing γδ T cells specifically localized to these areas. Functionally, recombinant IL-17A and conditioned media from γδ T cells enhanced alkaline phosphatase (ALP) activity and mineral deposition in HDPSCs, as shown by ALP and Alizarin Red staining. Additionally, qPCR revealed upregulation of dentinogenic markers, particularly ALP, following exposure to γδ T cell-derived factors. These effects were accompanied by increased mineral nodule formation, suggesting that IL-17A acts as a pro-calcific cytokine in the pulp microenvironment. Collectively, these findings indicate that γδ T cells infiltrate the dental pulp and actively contribute to tissue calcification by secreting IL-17A, suggesting a novel immunoregulatory role in dental pulp repair and regeneration. This insight may have clinical relevance in modulating inflammation-induced pulp healing and promoting dentin bridge formation in endodontic therapies.