The correlation between the Th17/Treg cell balance and bone health

Zhu, Lei; Fang, Hua; Ding, Wenge; Ding, Kai; Zhang, Yige; Xu, Chenyang

doi:10.1186/s12979-020-00202-z

Cited by 75 publications

(47 citation statements)

References 99 publications

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“…Conversely, Treg cells can secrete anti-inflammatory cytokines IL-10 and TGF-β, inhibit T cells and antigen presentation cells, and exert an immunosuppressive effect by reducing the proinflammatory cytokines secretion [47]. TGF-β influences the differentiation of 17 cells and participates in regulating Treg functions, especially to maintain the balance of 17/Treg [48]. e expression levels of TNF-α, IL-1, and IL-6 in the joint tissues of the CIA model group in the current study were markedly higher than those of the blank group.…”

Section: Discussionmentioning

confidence: 99%

Wu-Teng-Gao External Treatment Improves Th17/Treg Balance in Rheumatoid Arthritis

Yao

Wang

Chen

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Rheumatoid arthritis (RA) represents the consequence of an immune response of the body’s immune system attacking healthy cells. This chronic inflammatory disorder has complicated pathogenesis. Traditional Chinese medicine (TCM) is well recognized as an effective therapy in treating RA and has been widely applied for centuries. Wu-Teng-Gao (WTG) is used as a representative natural herb formula in RA treatment in China, while its mechanisms are to be fully clarified. The present study attempted to explore mechanisms of WTG on RA treatment in a network pharmacological approach and verified using experiments in vitro. Following the establishment of a rat model of collagen-induced arthritis (CIA), WTG was applied externally on the metapedes of rats. HE staining was subsequently performed to visualize the pathological changes of synovium and bone. Simultaneously, flow cytometry was conducted to detect the cell ratio of T helper 17 (Th17) and Regulatory T cells (Treg) in splenic lymphocytes. Additionally, ELISA, qRT-PCR, and Western blot assays were adopted to determine expressions of RA-related factors in joints and serum. Results of network pharmacological analysis suggested that Th17 cell differentiation might serve as a potential signaling pathway of WTG therapy for RA. Animal experiments demonstrated that WTG ameliorated the articular inflammation and effectively inhibited the destruction of articular cartilage, and decreased Th17 and Treg cell ratios in CIA rats. Furthermore, WTG also greatly suppressed relevant levels of inflammatory cytokines (IL-17, TNF-α, IL-1, and IL-6) and RNAKL, whereas it elevated expressions of anti-inflammatory cytokines IL-10 and TGF-β. Our results confirmed that WTG might improve the imbalance of Th17/Treg cells in CIA animals through differentiation regulation, thus alleviating joint inflammation and bone destruction.

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Section: Discussionmentioning

confidence: 99%

Wu-Teng-Gao External Treatment Improves Th17/Treg Balance in Rheumatoid Arthritis

Yao

Wang

Chen

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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“…The Foxo signaling pathway acts as an important role in regulating bone cell functions and bone health; for example, Foxo promotes normal skeletal development in chondrocytes but decreases bone resorption and formation in osteoclasts ( Kim et al, 2018 ; Ma et al, 2020 ). It is known to us that regulatory T (Treg) cells and T helper 17 (Th17) cells play crucial roles in maintaining bone homeostasis, and Th17 cells promote osteoclast differentiation, which contribute to OP ( Zhu et al, 2020 ). Maintaining the balance between Treg and Th17 cells may provide a novel promising strategy for treatment of OP ( Yang et al, 2021b ; Sapra et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology and Molecular Docking Elucidate the Pharmacological Mechanism of the OSTEOWONDER Capsule for Treating Osteoporosis

Fan

Zhou

et al. 2022

Front. Genet.

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Background: Osteoporosis (OP) is a serious and common bone metabolic disease with bone mass loss and bone microarchitectural deterioration. The OSTEOWONDER capsule is clinically used to treat OP. However, the potential regulatory mechanism of the OSTEOWONDER capsule in treatment of OP remains largely unknown.Methods: The bioactive compounds of herbs and their targets were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database. The speculative targets of OP were screened out based on GeneCards, DisGeNET, and Online Mendelian Inheritance in Man (OMIM) databases. The gene modules and hub genes of OP were identified using a weighted gene co-expression network analysis (WGCNA). Then, an herb-compound-target network was constructed based on the above analyses. The biological function of targets was subsequently investigated, and a protein–protein interaction (PPI) network was constructed to identify hub targets of OP. Finally, molecular docking was performed to explore the interaction between compounds and targets.Results: A total of 148 compounds of eight herbs and the corresponding 273 targets were identified based on the TCMSP database. A total of 4,929 targets of OP were obtained based on GeneCards, DisGeNET, and OMIM databases. In addition, six gene modules and 4,235 hub genes of OP were screened out based on WGCNA. Generally, an herb-compound-target network, including eight herbs, 84 compounds, and 58 targets, was constructed to investigate the therapeutic mechanism of the OSTEOWONDER capsule for OP. The biofunction analysis indicated 58 targets mainly associated with the bone metabolism, stimulation response, and immune response. EGFR, HIF1A, MAPK8, IL6, and PPARG were identified as the hub therapeutic targets in OP. Moreover, the interaction between EGFR, HIF1A, MAPK8, IL6, PPARG, and the corresponding compounds (quercetin and nobiletin) was analyzed using molecular docking.Conclusion: Our finding discovered the possible therapeutic mechanisms of the OSTEOWONDER capsule and supplied the potential therapeutic targets for OP.

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“…37,54,67 This could be due to the central role played by the TGFβ cytokine in establishment of balance between T H 17 and Treg cell differentiation. 68,69 This suggests suppression of the adaptive immune response during the early stages of infestation which may result in uncontrolled mite proliferation and subsequent activation of deleterious pro-inflammatory immune responses in later phases of CS development.…”

Section: Cellular Responsementioning

confidence: 99%

“…This suggests a central importance for the TGFβ cytokine since it is involved in differentiation of both T H 17 and Treg cells in the presence and absence of pro-inflammatory factors, respectively. 68,69 On the other hand, in contrast to CS, mite proliferation is kept under control in OS by the initiation of an early mixed T H 1/T H 2-mediated immune response with increased production of cytokines including IFNγ, but with lower level of antibody production and more dependency on CD4 + T-cells.…”

Section: Con Clus I On S and Future S Tud Ie Smentioning

confidence: 99%

Immune mechanisms in humanSarcoptes scabiei(Acari: Sarcoptidae) infestations

Gazi

Taylan-Özkan

Mumcuoglu³

2021

Parasite Immunology

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Scabies is a parasitic infestation of human and animal skin caused by different strains of the itch mite, Sarcoptes scabiei. The World Health Organization (WHO) has declared scabies in human as a neglected tropical disease, and today over 200 million people worldwide are affected. The two most commonly reported clinical manifestation of the condition are ordinary (OS) and crusted scabies (CS). CS, which can lead to fatal consequences due to secondary bacterial infections, is mostly observed in immunocompromised subjects but can also, although rarely, be detected in immunocompetent individuals. Innate and adaptive immune system components are involved in protection and pathogenesis of scabies, although with some differences between OS and CS. While the cutaneous immune response is dominated by CD4 + T-cells in OS, it is mainly mediated by CD8 + T-cells in CS. The two clinical conditions also differ in CD4 + T-cell-mediated immune responses with mixed T H 1/T H 2 (protective) and T H 2/T H 17 (non-protective) immunoprofiles in OS and CS, respectively. Moreover, the development of CS is associated with early immunosuppression that is followed by deleterious immune response to uncontrolled mite proliferation. However, the immune response to scabies still needs further attention due to inconsistent results in the literature. The aim of this study is to attract more attention to this area by summarizing the current literature on innate and adaptive immune responses triggered against S. scabiei mites.

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The correlation between the Th17/Treg cell balance and bone health

Cited by 75 publications

References 99 publications

Wu-Teng-Gao External Treatment Improves Th17/Treg Balance in Rheumatoid Arthritis

Wu-Teng-Gao External Treatment Improves Th17/Treg Balance in Rheumatoid Arthritis

Network Pharmacology and Molecular Docking Elucidate the Pharmacological Mechanism of the OSTEOWONDER Capsule for Treating Osteoporosis

Immune mechanisms in humanSarcoptes scabiei(Acari: Sarcoptidae) infestations

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