Treg: A Promising Immunotherapeutic Target in Oral Diseases.

Yujing Zhang,Rong Jia,Jihua Guo

doi:10.3389/fimmu.2021.667862

Abstract

With the pandemic of COVID-19, maintenance of oral health has increasingly become the main challenge of global health. Various common oral diseases, such as periodontitis and oral cancer, are closely associated with immune disorders in the oral mucosa. Regulatory T cells (Treg) are essential for maintaining self-tolerance and immunosuppression. During the process of periodontitis and apical periodontitis, two typical chronic immune-inflammatory diseases, Treg contributes to maintain host immune homeostasis and minimize tissue damage. In contrast, in the development of oral precancerous lesions and oral cancer, Treg is expected to be depleted or down-regulated to enhance the anti-tumor immune response. Therefore, a deeper understanding of the distribution, function, and regulatory mechanisms of Treg cells may provide a prospect for the immunotherapy of oral diseases. In this review, we summarize the distribution and multiple roles of Treg in different oral diseases and discuss the possible mechanisms involved in Treg cell regulation, hope to provide a reference for future Treg-targeted immunotherapy in the treatment of oral diseases.

Highlights

Regulatory T cell (Treg) was first reported to be involved in maintaining self-tolerance as early as the 1970s, but there was still a lack of specific molecular markers [1]
The expansion of Treg cells attenuates lesion progression via the injection of cytokine C-C motif ligand 22 (CCL22)-releasing particles in the root canal system in a chemokine receptor type 4 (CCR4)-dependent manner [58]. These findings suggest that Treg chemoattractant application may be a promising option in the treatment of apical periodontitis
In the A. actinomycetemcomitans induced mice model of periodontitis, inhibiting the function of Treg cells by anti-GITR resulted in alveolar bone resorption and increased inflammatory cell infiltration, accompanied by the decrease of IL-10, TGF-b, and cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) [70]

Summary

Introduction

Regulatory T cell (Treg) was first reported to be involved in maintaining self-tolerance as early as the 1970s, but there was still a lack of specific molecular markers [1]. Pro-inflammatory cytokines tumor necrosis factor-a (TNF-a) could down-regulate the expression of FOXP3 by binding with tumor necrosis factor receptor RII (TNFRII) and interfere with the inhibitory function of Treg cells [32]. Inhibition of Treg function with anti-GITR (a phenotypic marker of Treg cells) in mice impelled the exacerbation of severity of periapical lesions at 14 and 21 days, increased expression of pro-inflammatory cytokines and destructive tissue mediators, preventing the formation of the inactive/stable status.

Results

Conclusion