Treg: A Promising Immunotherapeutic Target in Oral Diseases

Zhang, Yujing; Guo, Jihua; Jia, Rong

doi:10.3389/fimmu.2021.667862

“…Treg cells can control immune response in both effector and inductive sites, as represented in Figure 1. Foxp3+ Treg cells are activated in lymphoid structures under inflammatory conditions and then recruited to effector site by specific combinations of chemotactic molecules [23,24]. The CCL22-CCR4 axis seems to be particularly relevant to the recruitment of Tregs cells, as shown in mice periodontitis models [25].…”

Section: Tolerance Mediated By Regulatory T Cellsmentioning

confidence: 98%

Immune Tolerance in the Oral Mucosa

Pelaez-Prestel

¹

,

Sanchez-Trincado

²

,

Lafuente

³

et al. 2021

IJMS

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The oral mucosa is a site of intense immune activity, where a large variety of immune cells meet to provide a first line of defense against pathogenic organisms. Interestingly, the oral mucosa is exposed to a plethora of antigens from food and commensal bacteria that must be tolerated. The mechanisms that enable this tolerance are not yet fully defined. Many works have focused on active immune mechanisms involving dendritic and regulatory T cells. However, epithelial cells also make a major contribution to tolerance by influencing both innate and adaptive immunity. Therefore, the tolerogenic mechanisms concurring in the oral mucosa are intertwined. Here, we review them systematically, paying special attention to the role of oral epithelial cells.

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“…Recent studies have focused on Th17 and Treg cells, which have opposite roles in the immune response in periapical lesions (Toledo et al, 2019). Treg and Th17 cells are thought to be important junctions between the immune system and bone (Zhang et al, 2021). According to a recent review, IL-17 and TNF-a secreted by Th17 cells promote RANKL expression and osteoclast differentiation, while TGF-b and IL-10 secreted by Treg cells inhibit this process (Wei et al, 2021).…”

Section: T Cellsmentioning

confidence: 99%

Mechanisms of bone remodeling and therapeutic strategies in chronic apical periodontitis

Xu-tao

¹

,

Wan

²

,

Liu

³

et al. 2022

Front. Cell. Infect. Microbiol.

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Chronic periapical periodontitis (CAP) is a typical oral disease in which periodontal inflammation caused by an odontogenic infection eventually leads to bone loss. Uncontrolled infections often lead to extensive bone loss around the root tip, which ultimately leads to tooth loss. The main clinical issue in the treatment of periapical periodontitis is the repair of jawbone defects, and infection control is the first priority. However, the oral cavity is an open environment, and the distribution of microorganisms through the mouth in jawbone defects is inevitable. The subversion of host cell metabolism by oral microorganisms initiates disease. The presence of microorganisms stimulates a series of immune responses, which in turn stimulates bone healing. Given the above background, we intended to examine the paradoxes and connections between microorganisms and jaw defect repair in anticipation of new ideas for jaw defect repair. To this end, we reviewed the microbial factors, human signaling pathways, immune cells, and cytokines involved in the development of CAP, as well as concentrated growth factor (CGF) and stem cells in bone defect repair, with the aim of understanding the impact of microbial factors on host cell metabolism to inform the etiology and clinical management of CAP.

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“…Th17 cells are an important subset of effector T cells that are protective during extracellular bacterial and fungal invasion [90][91][92][93][94]. Treg cells are essential for maintaining self-tolerance and immunosuppression [95]. As discussed above, probably due to the reduction in oral clearance and local antibodies or antimicrobial peptides, several opportunistic pathogens are proportionally enriched in old mice.…”

Section: Crosstalk Between the Oral Microbiota And Immune Cells With ...mentioning

confidence: 99%

The niche-specialist and age-related oral microbial ecosystem: crosstalk with host immune cells in homeostasis

Lin

¹

,

Hu

²

,

Yang

³

et al. 2022

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Although characterization of the baseline oral microbiota has been discussed, the current literature seems insufficient to draw a definitive conclusion on the interactions between the microbes themselves or with the host. This study focuses on the spatial and temporal characteristics of the oral microbial ecosystem in a mouse model and its crosstalk with host immune cells in homeostasis. The V3V4 regions of the 16S rRNA gene of 20 samples from four niches (tongue, buccal mucosa, keratinized gingiva and hard palate) and 10 samples from two life stages (adult and old) were analysed. Flow cytometry (FCM) was used to investigate the resident immune cells. The niche-specialist and age-related communities, characterized based on the microbiota structure, interspecies communications, microbial functions and interactions with immune cells, were addressed. The phylum Firmicutes was the major component in the oral community. The microbial community profiles at the genus level showed that the relative abundances of the genera Bacteroides , Lactobacillus and Porphyromonas were enriched in the gingiva. The abundance of the genera Streptococcus , Faecalibaculum and Veillonella was increased in palatal samples, while the abundance of Neisseria and Bradyrhizobium was enriched in buccal samples. The genera Corynebacterium , Stenotrophomonas, Streptococcus and Fusobacterium were proportionally enriched in old samples, while Prevotella and Lacobacillus were enriched in adult samples. Network analysis showed that the genus Lactobacillus performed as a central node in the buccal module, while in the gingiva module, the central nodes were Nesterenkonia and Hydrogenophilus . FCM showed that the proportion of Th1 cells in the tongue samples (38.18 % [27.03–49.34 %]) (mean [range]) was the highest. The proportion of γδT cells in the buccal mucosa (25.82 % [22.1–29.54 %]) and gingiva (20.42 % [18.31–22.53 %]) samples was higher (P<0.01) than those in the palate (14.18 % [11.69–16.67 %]) and tongue (9.38 % [5.38–13.37 %] samples. The proportion of Th2 (31.3 % [16.16–46.44 %]), Th17 (27.06 % [15.76–38.36 %]) and Treg (29.74 % [15.71–43.77 %]) cells in the old samples was higher than that in the adult samples (P<0.01). Further analysis of the interplays between the microbiomes and immune cells indicated that Th1 cells in the adult group, nd Th2, Th17 and Treg cells in the old group were the main immune factors strongly associated with the oral microbiota. For example, Th2, Th17 and Treg cells showed a significantly positive correlation with age-related microorganisms such as Sphingomonas , Streptococcus and Acinetobacter , while Th1 cells showed a negative correlation. Another positive correlation occurred between Th1 cells and several commensal microbiomes such as Lactobacillus , Jeotgalicoccus and Sporosarcina . Th2, Th17 and Treg cells showed the opposite trend. Together, our findings identify the niche-specialist and age-related characteristics of the oral microbial ecosystem and the potential associations between the microbiomes and the mucosal immune cells, providing critical insights into mucosal microbiology.

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Treg: A Promising Immunotherapeutic Target in Oral Diseases

Cited by 24 publications

References 158 publications

Immune Tolerance in the Oral Mucosa

Immune Tolerance in the Oral Mucosa

Mechanisms of bone remodeling and therapeutic strategies in chronic apical periodontitis

The niche-specialist and age-related oral microbial ecosystem: crosstalk with host immune cells in homeostasis

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