Rojas, Carolina, Gonzalez-Osuna, Luis, Garcia, Michelle, Sierra-Cristancho, Alfredo, Sansores-Espana, Luis Daniel, Carvajal, Paola, Smyth, Lesley, Pino-Lagos, Karina and Vernal, Rolando (2026) Targeting periodontitis with Treg-derived extracellular vesicles: modulation of Macrophages and CD8+ T-cell responses. International Journal of Molecular Sciences, 27 (13).

Preview

PDF/A SmythLA_Targeting Periodontitis with Treg-Derived Extracellular Vesicles Modulation of Macrophages and CD8+ T-Cell Responses_PDFA.pdf - Published Version Available under License Creative Commons Attribution. Download (4MB) | Preview

Abstract

Periodontitis is a chronic inflammatory disease characterized by alveolar bone loss driven by dysregulated immune responses. We previously showed that extracellular vesicles derived from retinoic acid-induced regulatory T lymphocytes (RA-Treg EVs) suppress pathogenic CD4+ T-lymphocyte responses and reduce alveolar bone loss during periodon- titis. Herein, we investigated whether RA-Treg EVs also modulate macrophage and CD8+ T-lymphocyte responses during experimental periodontitis. Ligature-induced periodontitis was generated in mice, followed by local administration of RA-Treg EVs. Alveolar bone loss was analyzed by micro-computed tomography, and periodontal tissues and cervi- cal lymph nodes were analyzed by flow cytometry to quantify antigen-presenting cells, macrophages, macrophage subsets, and CD8+ T lymphocytes. The direct effects of RA-Treg EVs on macrophage phenotype and CD8+ T-cell proliferation and activation were assessed in vitro. RA-Treg EV treatment attenuated alveolar bone loss and preserved trabecular microarchitecture. This effect was associated with reduced macrophage infiltration into periodontal tissues, modulation of macrophage polarization, and restoration of CD8+ T- cell abundance in periodontal tissues and draining cervical lymph nodes, without major changes in CD8+IFN-γ+ or CD8+RANKL+ cells. In vitro, RA-Treg EVs induced heteroge- neous macrophage phenotypes distinct from the classical M1/M2 polarization states while markedly enhancing CD8+ T-cell proliferation and activation. These findings indicate that RA-Treg EVs preserve alveolar bone during experimental periodontitis while selectively modulating macrophage and CD8+ T-lymphocyte responses.

Item Type:	Article
Identifier:	10.3390/ijms27135845
Keywords:	extracellular vesicles; periodontitis; regulatory T cell; Treg; alveolar bone loss; macrophages; CD8+ T lymphocytes
Subjects:	Medicine and health > Microbiology
Date Deposited:	01 Jul 2026
Dates:	Date Publication status 22 June 2026 Accepted 29 June 2026 Published
School, department or research centre:	School of Medicine and Biosciences
Keywords:	extracellular vesicles; periodontitis; regulatory T cell; Treg; alveolar bone loss; macrophages; CD8+ T lymphocytes
URI:	https://repository.uwl.ac.uk/id/eprint/15221
Sustainable Development Goals:	Goal 3: Good Health and Well-Being

Downloads

Actions (admin access)