γδT Cells Are Essential for Orthodontic Tooth Movement

Abstract

Sustained mechanical forces applied to tissue are known to shape local immunity. In the oral mucosa, mechanical stress, either naturally induced by masticatory forces or externally via mechanical loading during orthodontic tooth movement (OTM), is translated, in part, by T cells to alveolar bone resorption. Nevertheless, despite being considered critical for OTM, depletion of CD4+ and CD8+ T cells is reported to have no impact on tooth movement, thus questioning the function of αβT cells in OTM-associated bone resorption. To further address the role of T cells in OTM, we first characterized the leukocytes residing in the periodontal ligament (PDL), the tissue of interest during OTM, and compared it to the neighboring gingiva. Unlike the gingiva, monocytes and neutrophils represent the major leukocytes of the PDL. These myeloid cells were also the main leukocytes in the PDL of germ-free mice, although at lower levels than SPF mice. T lymphocytes were more enriched in the gingiva than the PDL, yet in both tissues, the relative fraction of the γδT cells was higher than the αβ T cells. We thus sought to examine the role of γδT cells in OTM. γδT cells residing in the PDL were mainly Vγ6+ and produced interleukin (IL)–17A but not interferon-γ. Using Tcrd-GDL mice allowing conditional ablation of γδT cells in vivo, we demonstrate that OTM was greatly diminished in the absence of γδT cells. Further analysis revealed that ablation of γδT cells decreased early IL-17A expression, monocyte and neutrophil recruitment, and the expression of the osteoclastogenic molecule receptor activator of nuclear factor–κβ ligand. This, eventually, resulted in reduced numbers of osteoclasts in the pressure site during OTM. Collectively, our data suggest that γδT cells are essential in OTM for translating orthodontic mechanical forces to bone resorption, required for relocating the tooth in the alveolar bone.

Immune Changes Induced by Orthodontic Forces: A Critical Review

“…The significantly increased percentage of B and CD3 + cells reported by Wald et al (2021) after 14 d indicates a role for adaptive immunity at this stage. The percentage of neutrophils, monocytes, and γδT and CD4 + T cells significantly decreased but remained higher than their baseline values.…”

“…In steady state, the immune cells that reside in mouse PDL consist of ~70% neutrophils and monocytes; the remainder are antigen-presenting cells (APCs) and lymphocytes (Wald et al 2021). The acute inflammatory reaction evokes a typical innate immune response.…”

“…Recently, Wald et al (2021) proved that γδT cells participate in OTM. Although their percentage in the initial phase remained low, ablation of γδT cells significantly reduced the production of IL-17A and OTM, suggesting their role as tissue resident cells that quickly respond to the mechanical threat.…”

“…The main events in resolution are cessation of neutrophil influx and macrophage clearance of necrotic tissue debris. Wald et al (2021) showed that the percentage of monocytes and activated neutrophils decreases, and Klein et al (2020) reported downregulation of pathways related to granulocyte and agranulocyte adhesion and diapedesis after peaking at day 3.…”

“…In contrast, the percentage of γδT cells (Wald et al 2021) and Treg cells significantly increases during this period, in parallel to a decrease in CD4 + , Th1, and Th17 T cells (Li et al 2020). Pathways related to crosstalk between dendritic and NK cells are downregulated, and B-cell development is upregulated (Klein et al 2020).…”