Characterization of the Protective Role of Regulatory T Cells in Experimental Periapical Lesions Development and Its Chemoattraction Manipulation as a Therapeutic Tool

Authors

Carolina Favaro Francisconi
Andreia Espindola Vieira
Cláudia Cristina Biguetti, The University of Texas Rio Grande ValleyFollow
Andrew J. Glowacki
Ana Paula Favaro Trombone
Ariadne Letra
Renato Menezes Silva
Charles S. Sfeir
Steven R. Little
Gustavo P. Garlet

Document Type

Article

Publication Date

1-2016

Abstract

Introduction

The pathogenesis of periapical lesions is determined by the balance between host pro-inflammatory immune response and counteracting anti-inflammatory and reparative responses, which include regulatory T cells (Tregs) as potential immunoregulatory agents. In this study, we investigated (in a cause-and-effect manner) the involvement of CCL22-CCR4 axis in Tregs migration to the periapical area and the role of Tregs in the determination of outcomes in periapical lesions.

Methods

Periapical lesions were induced in C57Bl/6 (WT) and CCR4KO mice (pulp exposure and bacterial inoculation), and treated with anti-GITR to inhibit Tregs function or alternatively with CCL22-releasing, PLGA particles to induce site-specific migration of Tregs. Post treatment, lesions were analyzed for Tregs influx and phenotype, overall periapical bone loss and inflammatory/immunological and wound healing markers expression (analyzed by RealTimePCRarray).

Results

Tregs inhibition by anti-GITR or CCR4 depletion results in a significant increase in periapical lesions severity, associated with upregulation of proinflammatory, Th1, Th17 and tissue destruction markers in parallel with decreased Tregs and healing markers expression. The local release of CCL22 in the root canal system resulted in the promotion of Tregs migration in a CCR4-dependent manner, leading to the arrest of periapical lesions progression, associated with downregulation of pro-inflammatory, Th1, Th17 and tissue destruction markers in parallel with increased Tregs and healing markers expression.

Conclusions

Since the natural and CCL22 induced Tregs migration switch active lesion into inactivity phenotype, Tregs chemoattractant may be a promisor strategy for the clinical management of periapical lesions.

Comments

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Recommended Citation

Francisconi, C. F., Vieira, A. E., Biguetti, C. C., Glowacki, A. J., Trombone, A. P., Letra, A., Menezes Silva, R., Sfeir, C. S., Little, S. R., & Garlet, G. P. (2016). Characterization of the Protective Role of Regulatory T Cells in Experimental Periapical Lesion Development and Their Chemoattraction Manipulation as a Therapeutic Tool. Journal of endodontics, 42(1), 120–126. https://doi.org/10.1016/j.joen.2015.09.022

Publication Title

Journal of endodontics

Academic Level

faculty

DOI

https://doi.org/10.1016/j.joen.2015.09.022