γδT Cells Are Essential for Orthodontic Tooth Movement

S. Wald, A. Leibowitz, Y. Aizenbud, Y. Saba, K. Zubeidat, O. Barel, N. Koren, O. Heyman, A. Wilharm, I. Sandrock, O. Fleissig, Y. Tal, I. Prinz, D. Aizenbud, S. Chaushu, A. H. Hovav*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

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.

Original languageAmerican English
Pages (from-to)731-738
Number of pages8
JournalJournal of Dental Research
Volume100
Issue number7
DOIs
StatePublished - Jul 2021

Bibliographical note

Publisher Copyright:
© International & American Associations for Dental Research 2021.

Keywords

  • Interleukin-17 (IL-17)
  • bone resorption
  • innate immunity
  • oral mucosa
  • osteoclasts
  • periodontal ligament

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