The imbalance of Th17/Treg via STAT3 activation modulates cognitive impairment in<i>P. gingivalis</i> LPS-induced periodontitis mice

Zhang, Xu; Zhang, Xuan; Qiu, Che; Shen, Hui; Zhang, Huanyu; He, Zhaojian; Zhang, Song; Wei, Zhou

doi:10.1002/jlb.3ma0521-742rrr

Cited by 20 publications

(34 citation statements)

References 53 publications

(105 reference statements)

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“…Recently, it has been shown that a particular subset of Tfh cells infiltrate the brain of mice suffering systemic lupus erythematosus, thereby possibly contributing to the neuropsychiatric manifestations (memory impairment, cognitive deficits and mood disturbance) of this disease (80). Some of these symptoms are also present in anxiety, mood and trauma and stress-related disorders (81).…”

Section: Findings In Non-human Primatesmentioning

confidence: 99%

“…Even if the use of ligatures to induce periodontitis has demonstrated more severe periodontal destruction in shorter time, oral gavages with periodontal pathogens or their endotoxins (such as LPS) are more representative of the physiopathology of periodontitis (84). LPS-induced periodontitis may promote the occurrence and progression of learning and memory impairment by modulating the T helper 17 (Th17)/regulatory T cell (Treg) balance in a mechanism related to the STAT3 signaling pathway (81). In a similar way, C57BL/6 mice injected with P. gingivalis exhibited impaired spatial learning and memory during the Morris Water Maze test and exhibited attenuated passive avoidance learning, effects that were mediated by the activation of the toll-like receptor (TLR) 4 pro-inflammatory signaling pathway (85).…”

Section: Findings In Rodentsmentioning

confidence: 99%

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The Role of the Oral Microbiota Related to Periodontal Diseases in Anxiety, Mood and Trauma- and Stress-Related Disorders

et al. 2022

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The prevalence of anxiety, mood and trauma- and stress-related disorders are on the rise; however, efforts to develop new and effective treatment strategies have had limited success. To identify novel therapeutic targets, a comprehensive understanding of the disease etiology is needed, especially in the context of the holobiont, i.e., the superorganism consisting of a human and its microbiotas. Much emphasis has been placed on the role of the gut microbiota in the development, exacerbation, and persistence of psychiatric disorders; however, data for the oral microbiota are limited. The oral cavity houses the second most diverse microbial community in the body, with over 700 bacterial species that colonize the soft and hard tissues. Periodontal diseases encompass a group of infectious and inflammatory diseases that affect the periodontium. Among them, periodontitis is defined as a chronic, multi-bacterial infection that elicits low-grade systemic inflammation via the release of pro-inflammatory cytokines, as well as local invasion and long-distance translocation of periodontal pathogens. Periodontitis can also induce or exacerbate other chronic systemic inflammatory diseases such as atherosclerosis and diabetes and can lead to adverse pregnancy outcomes. Recently, periodontal pathogens have been implicated in the etiology and pathophysiology of neuropsychiatric disorders (such as depression and schizophrenia), especially as dysregulation of the immune system also plays an integral role in the etiology and pathophysiology of these disorders. This review will discuss the role of the oral microbiota associated with periodontal diseases in anxiety, mood and trauma- and stress-related disorders. Epidemiological data of periodontal diseases in individuals with these disorders will be presented, followed by a discussion of the microbiological and immunological links between the oral microbiota and the central nervous system. Pre-clinical and clinical findings on the oral microbiota related to periodontal diseases in anxiety, mood and trauma- and stress-related phenotypes will be reviewed, followed by a discussion on the bi-directionality of the oral-brain axis. Lastly, we will focus on the oral microbiota associated with periodontal diseases as a target for future therapeutic interventions to alleviate symptoms of these debilitating psychiatric disorders.

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Section: Findings In Non-human Primatesmentioning

confidence: 99%

Section: Findings In Rodentsmentioning

confidence: 99%

The Role of the Oral Microbiota Related to Periodontal Diseases in Anxiety, Mood and Trauma- and Stress-Related Disorders

et al. 2022

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“…Other subsets of T regs were defined based on cell phenotype and characteristic markers, secreted cytokines and chemokines and specific immune regulation functions ( Table 1 ) ( 43 , 48 ). These include Resting T regs (rT regs ), Activated T regs (aT regs ), Non-suppressive T regs (non-T regs ) and helper-like T regs (Th-T regs ), and three recently discovered Foxp3-T regs .…”

Section: Sae and Regulatory T Cellsmentioning

confidence: 99%

“…Based on their origin, T regs can be divided into two subsets: thymus-derived T regs (tT regs ) and peripheral-derived T regs (pT regs ) (40)(41)(42)(43). tT regs (44) are characterized by their constitutive expression of Foxp3 and stable suppressive function, whereas pT regs (45) exhibit unstable Foxp3 expression, unstable suppressive function and can differentiate into cells with an effector function.…”

Section: Sae and Regulatory T Cellsmentioning

confidence: 99%

“…In a study conducted by Drechsler et al it was demonstrated that pT regs , rather than tT regs , may play a role in improving septic survival (46). Increasing evidence, directly or indirectly, confirmed that pT regs and brain-specific T regs are involved in the acute and chronic phase of SAE by mitigating Other subsets of T regs were defined based on cell phenotype and characteristic markers, secreted cytokines and chemokines and specific immune regulation functions (Table 1) (43,48). These include Resting T regs (rT regs ), Activated T regs (aT regs ), Non-suppressive T regs (non-T regs ) and helper-like T regs (Th-T regs ), and three recently discovered Foxp3-T regs .…”

Section: Sae and Regulatory T Cellsmentioning

confidence: 99%

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Insight Into Regulatory T Cells in Sepsis-Associated Encephalopathy

et al. 2022

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Sepsis-associated encephalopathy (SAE) is a diffuse central nervous system (CNS) dysfunction during sepsis, and is associated with increased mortality and poor outcomes in septic patients. Despite the high incidence and clinical relevance, the exact mechanisms driving SAE pathogenesis are not yet fully understood, and no specific therapeutic strategies are available. Regulatory T cells (Tregs) have a role in SAE pathogenesis, thought to be related with alleviation of sepsis-induced hyper-inflammation and immune responses, promotion of T helper (Th) 2 cells functional shift, neuroinflammation resolution, improvement of the blood-brain barrier (BBB) function, among others. Moreover, in a clinical point of view, these cells have the potential value of improving neurological and psychiatric/mental symptoms in SAE patients. This review aims to provide a general overview of SAE from its initial clinical presentation to long-term cognitive impairment and summarizes the main features of its pathogenesis. Additionally, a detailed overview on the main mechanisms by which Tregs may impact SAE pathogenesis is given. Finally, and considering that Tregs may be a novel target for immunomodulatory intervention in SAE, different therapeutic options, aiming to boost peripheral and brain infiltration of Tregs, are discussed.

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Molecular Basis of the Curative Effects of Turkish Gall Extracts on Periodontitis

2024

ChemistrySelect

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We explored the mechanism whereby Turkish gall extracts prevent and effectively cure periodontitis. Main bioactive components were obtained from previous reports and targets were screened using TCMSP, PubChem, SwissTargetPrediction, and Drugbank databases. Chronic periodontitis targets were retrieved from OMIM, GeneCards, and DisGeNET databases. Intersectional targets of Turkish galls and periodontitis were obtained using Venn analysis. String databases were used to construct a protein–protein interaction network of common targets. R language was used for GO and KEGG enrichment analyses of common targets. Molecular docking analysis confirmed Turkish gall extract effectiveness for periodontitis treatment, which was verified in vitro and inhibited MAPK1, MAPK3 and SRC expression. We predicted 759 possible target genes. Among 2059 identified periodontitis genes, 205 overlapped with those in methanolic Turkish gall extract. Key targets included JUN, tumor protein 53, MAPK1, MAPK3, STAT3, RELA, and SRC. GO analysis showed that common targets were mainly involved in processes such as oxidative stress. KEGG analysis indicated that common targets were enriched in 163 pathways. Molecular docking analysis showed that 1,2,3,6‐tetra‐O‐galloyl‐β‐D‐glucose, 1,3,6‐tri‐O‐galloyl‐β‐D‐glucose and 1,2,3,4,6‐penta‐O‐galloyl‐β‐D‐glucose were strongly associated with MAPK1, MAPK3, and SRC. Turkish gall extract reduced inflammation and targets expression in vitro, providing a reference for drug development for periodontitis.

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The imbalance of Th17/Treg via STAT3 activation modulates cognitive impairment inP. gingivalis LPS-induced periodontitis mice

Cited by 20 publications

References 53 publications

The Role of the Oral Microbiota Related to Periodontal Diseases in Anxiety, Mood and Trauma- and Stress-Related Disorders

The Role of the Oral Microbiota Related to Periodontal Diseases in Anxiety, Mood and Trauma- and Stress-Related Disorders

Insight Into Regulatory T Cells in Sepsis-Associated Encephalopathy

Molecular Basis of the Curative Effects of Turkish Gall Extracts on Periodontitis

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