Citrullination: A Specific Target for the Autoimmune Response in Rheumatoid Arthritis

Fox, David A.

doi:10.4049/jimmunol.1501021

Cited by 20 publications

(9 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Citrullination also play a critical role in RA pathogenesis [ 14 , 15 ]. Increased citrullination is observed in the RA synovium, and antibodies against citrullinated peptides are generated by RA-associated autoimmune responses [ 16 – 18 ]. Previous studies suggest that PAD mediates citrullination of proteins in RA as well [ 6 , 7 , 19 – 21 ].…”

Section: Introductionmentioning

confidence: 99%

Arthritic role of Porphyromonas gingivalis in collagen-induced arthritis mice

Jung

Rim

et al. 2017

PLoS ONE

View full text Add to dashboard Cite

Epidemiological studies show an association between rheumatoid arthritis (RA) and periodontal disease. Porphyromonas gingivalis (P.gingivalis) is a well-known pathogen in periodontitis. This study investigated the pathogenic effects of P.gingivalis on autoimmune arthritis in vivo. Collagen-induced arthritis (CIA) mice were intraperitoneally injected with W83 and 2561 strains of P.gingivalis. Infection with P.gingivalis exacerbated arthritis score in CIA mice. Synovial inflammation and bone destruction in CIA mice infected with P.gingivalis were more severe than in uninfected CIA mice. Both W83 and 2561 strains were more pro-arthritic after arthritis symptom was fully activated. Interestingly, only W83 strain was arthritogenic before autoimmune reaction initiated. Citrullination was detected in synovial tissue of CIA mice and CIA mice inoculated with P.gingivalis, but not in normal control mice. The citrullinated area was greater in P.gingivalis-infected CIA mice than in non-infected CIA mice. This study showed that P.gingivalis exacerbated disease in a mouse model of autoimmune arthritis and increased the expression of citrullinated antigens in the synovium. The arthritogenic effects of P.gingivalis were at least in part, dependent upon the bacterial strain with or without fimbriae expression, route and time of infection. P.gingivalis-mediated citrullination may explain the possible link between periodontal disease and RA.

show abstract

Section: Introductionmentioning

confidence: 99%

Arthritic role of Porphyromonas gingivalis in collagen-induced arthritis mice

Jung

Rim

et al. 2017

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…The proportion of Th17 cells in spleen T lymphocytes of CIA mice was signi cantly higher than that of WT mice. On the contrary, compared with normal mice, the pool of splenic Treg cells in CIA mice was slightly reduced, leading to an imbalance of Th17/Treg, which has been accepted as one of the important pathogenesis of RA [22,23]. Compared with CIA mice treated by vehicle, Ziyu I administration effectively reduces thymus index, T cell viability, plasma IL-17 concentration, and most importantly, the frequency of Th17 cell subset.…”

Section: Discussionmentioning

confidence: 98%

Ziyuglycoside I attenuates collagen-induced arthritis through restoring the balance of Th17/Treg cells

Wang

Sun

et al. 2022

Preprint

View full text Add to dashboard Cite

Objective: To investigate the therapeutic effect and primary pharmacological mechanism of Ziyuglycoside I (Ziyu I) on collagen-induced arthritis (CIA) mice. Methods: CIA mice were treated by 5, 10, or 20 mg/kg of Ziyu I or 2 mg/kg of methotrexate (MTX), and clinical manifestations as well as pathological changes were observed. T cell subsets were determined by flow cytometry. T cell viability was measured by CCK-8. The expressions of transforming growth factor beta (TGF-β) and IL-17 in serum were detected by Elisa. The mRNA expressions of RORγt and Foxp3 in mice spleen lymphocytes were detected by RT-qPCR. Molecular docking was used to detect whether there was a molecular interaction between Ziyu I and Akt. The activation of mTOR in T cells was verified by Western blotting or immunofluorescence. Results: Ziyu I treatment group could effectively alleviate the arthritis symptoms of CIA mice, including body weight, global score, arthritis index, number of swollen joints, etc. The pathological changes of joints and spleen in arthritic mice were improved effectively. The thymic index, T cell activity and RORγt production of Ziyu I treatment group were significantly reduced. Notably, through molecular docking, western blotting, and immunofluorescence analysis data, we found that Ziyu I could interact directly with Akt to reduce downstream mTOR activation and inhibit Th17 differentiation, thereby regulating Th17/Treg balance and improving arthritis symptoms. Conclusion: Our data showed that Ziyu I effectively improved arthritic symptoms of CIA in mice by inhibiting mTOR activation, thereby affecting Th17 differentiation and regulating Th17/Treg balance.

show abstract

“…As mentioned before, the secreted antibodies recognize the modified amino acid citrulline within the targeted protein, and these autoantibodies directed to the citrullinated peptides or proteins are known as anticitrullinated peptide antibodies (ACPA) [383]. The breakthrough of ACPA in 1960 was a very important discovery that helped in the diagnosis, organization, and treatment of the most common autoimmune disorders, especially rheumatoid arthritis (RA) [384, 385]. In the synovium of RA patients, multiple citrullinated proteins were detected to produce an antigenic peptide that can induce a humoral response and the subsequent production of autoantibodies.…”

Section: Citrullinated Proteins Are a Target For Circulating Autoamentioning

confidence: 99%

An Overview of the Intrinsic Role of Citrullination in Autoimmune Disorders

Alghamdi

Alasmari

Assiri

et al. 2019

Journal of Immunology Research

View full text Add to dashboard Cite

A protein undergoes many types of posttranslation modification. Citrullination is one of these modifications, where an arginine amino acid is converted to a citrulline amino acid. This process depends on catalytic enzymes such as peptidylarginine deiminase enzymes (PADs). This modification leads to a charge shift, which affects the protein structure, protein-protein interactions, and hydrogen bond formation, and it may cause protein denaturation. The irreversible citrullination reaction is not limited to a specific protein, cell, or tissue. It can target a wide range of proteins in the cell membrane, cytoplasm, nucleus, and mitochondria. Citrullination is a normal reaction during cell death. Apoptosis is normally accompanied with a clearance process via scavenger cells. A defect in the clearance system either in terms of efficiency or capacity may occur due to massive cell death, which may result in the accumulation and leakage of PAD enzymes and the citrullinated peptide from the necrotized cell which could be recognized by the immune system, where the immunological tolerance will be avoided and the autoimmune disorders will be subsequently triggered. The induction of autoimmune responses, autoantibody production, and cytokines involved in the major autoimmune diseases will be discussed.

show abstract

Citrullination: A Specific Target for the Autoimmune Response in Rheumatoid Arthritis

Cited by 20 publications

References 44 publications

Arthritic role of Porphyromonas gingivalis in collagen-induced arthritis mice

Arthritic role of Porphyromonas gingivalis in collagen-induced arthritis mice

Ziyuglycoside I attenuates collagen-induced arthritis through restoring the balance of Th17/Treg cells

An Overview of the Intrinsic Role of Citrullination in Autoimmune Disorders

Contact Info

Product

Resources

About