γδ17T Cells Hinder Mandibular Bone Defect Healing

Area of Science:

• Immunology
• Skeletal Biology
• Regenerative Medicine

Background:

• Bone fracture healing involves complex immune-skeletal interactions, with flat bones like the mandible presenting unique challenges.
• Mandibular fractures are common, complicated by oral microbiota and mechanical forces, impacting healing.
• The role of interleukin-17 (IL-17) and γδT cells in bone repair remains controversial.

Purpose of the Study:

• To investigate the role of IL-17-producing γδT cells (γδ17T cells) in mandibular defect healing.
• To determine if targeting γδ17T cells or IL-17 can enhance mandibular bone regeneration.

Main Methods:

• A murine model of mandibular drill hole defect was established for spontaneous healing studies.
• γδT cell depletion (Tcrd-GDL mice) and IL-17 genetic ablation (Il17af-/- mice) were employed.
• Leukocyte infiltration, RNA sequencing, and immunologic analyses were performed to assess healing kinetics and inflammatory responses.

Main Results:

• Mandibular defects healed within 3 weeks, with distinct leukocyte infiltration patterns over time.
• Depletion of γδT cells or IL-17 significantly accelerated mandibular healing kinetics.
• IL-17 deficiency reduced later inflammatory responses without affecting early neutrophil and monocyte recruitment, leading to faster repair.

Conclusions:

• IL-17-producing γδT cells delay mandibular fracture repair by hindering inflammation resolution.
• Targeting γδ17T cells or IL-17 presents a potential therapeutic strategy to improve bone regeneration in mandibular fractures.