γδ17T Cells Hinder Mandibular Bone Defect Healing

We thus sought to investigate their role in the repair process of a mandibular defect. Here, we developed a murine model where a 1.5-mm drill hole defect spontaneously healed within 3 wk. Analysis revealed rapid leukocyte infiltration at the defect site by day 3, predominantly neutrophils and inflammatory monocytes, with γδT cells and adaptive leukocytes accumulating later at days 7 and 14.

Depletion of γδT cells via Tcrd-GDL mice or genetic ablation of IL-17 in Il17af-/- mice accelerated the kinetics of mandibular healing. Bulk RNA sequencing and immunologic analysis revealed that while early recruitment of neutrophils and monocytes was unaffected in Il17af-/- mice, later inflammatory responses were diminished, resulting in accelerated repair. These findings suggest that IL-17–producing γδT cells (γδ17T cells) delay mandibular fracture repair by inhibiting inflammation resolution, thus prolonging the reparative phase.

Targeting γδ17T cells or IL-17 may thus represent therapeutic strategies to enhance bone regeneration, particularly in challenging clinical settings involving mandibular fractures.