Increased Circulating Follicular Treg Cells Are Associated With Lower Levels of Autoantibodies in Patients With Rheumatoid Arthritis in Stable Remission

2018 ◽  
Vol 70 (5) ◽  
pp. 711-721 ◽  
Author(s):  
Chen Liu ◽  
Dongwei Wang ◽  
Songsong Lu ◽  
Qinzhu Xu ◽  
Lei Zhao ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Treg Cells

Helios But Not CD226, TIGIT and Foxp3 is a Potential Marker for CD4 Treg Cells in Patients with Rheumatoid Arthritis

2018 ◽  
Author(s):  
Mengru Yang ◽  
Yan Liu ◽  
Biyao Mo ◽  
Youqiu Xue ◽  
Congxiu Ye ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Treg Cells ◽  
Potential Marker

scholarly journals Regulatory T Cells Fail to Suppress Fast Homeostatic Proliferation In Vitro

Life ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 245
Author(s):  
Daniil Shevyrev ◽  
Valeriy Tereshchenko ◽  
Elena Blinova ◽  
Nadezda Knauer ◽  
Ekaterina Pashkina ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Autoimmune Diseases ◽  
Peripheral Blood ◽  
Treg Cells ◽  
Homeostatic Proliferation ◽  
Suppressive Activity ◽  
Healthy Donors

Homeostatic proliferation (HP) is a physiological process that reconstitutes the T cell pool after lymphopenia involving Interleukin-7 and 15 (IL-7 and IL-15), which are the key cytokines regulating the process. However, there is no evidence that these cytokines influence the function of regulatory T cells (Tregs). Since lymphopenia often accompanies autoimmune diseases, we decided to study the functional activity of Tregs stimulated by HP cytokines from patients with rheumatoid arthritis as compared with that of those from healthy donors. Since T cell receptor (TCR) signal strength determines the intensity of HP, we imitated slow HP using IL-7 or IL-15 and fast HP using a combination of IL-7 or IL-15 with anti-CD3 antibodies, cultivating Treg cells with peripheral blood mononuclear cells (PBMCs) at a 1:1 ratio. We used peripheral blood from 14 patients with rheumatoid arthritis and 18 healthy volunteers. We also used anti-CD3 and anti-CD3 + IL-2 stimulation as controls. The suppressive activity of Treg cells was evaluated in each case by the inhibition of the proliferation of CD4+ and CD8+ cells. The phenotype and proliferation of purified CD3+CD4+CD25+CD127lo cells were assessed by flow cytometry. The suppressive activity of the total pool of Tregs did not differ between the rheumatoid arthritis and healthy donors; however, it significantly decreased in conditions close to fast HP when the influence of HP cytokines was accompanied by anti-CD3 stimulation. The Treg proliferation caused by HP cytokines was lower in the rheumatoid arthritis (RA) patients than in the healthy individuals. The revealed decrease in Treg suppressive activity could impact the TCR landscape during lymphopenia and lead to the proliferation of potentially self-reactive T cell clones that are able to receive relatively strong TCR signals. This may be another explanation as to why lymphopenia is associated with the development of autoimmune diseases. The revealed decrease in Treg proliferation under IL-7 and IL-15 exposure can lead to a delay in Treg pool reconstitution in patients with rheumatoid arthritis in the case of lymphopenia.

A novel upstream enhancer ofFOXP3, sensitive to methylation-induced silencing, exhibits dysregulated methylation in rheumatoid arthritis Treg cells

2014 ◽  
Vol 44 (10) ◽  
pp. 2968-2978 ◽  
Author(s):  
Alan Kennedy ◽  
Emily M. Schmidt ◽  
Adam P. Cribbs ◽  
Henry Penn ◽  
Parisa Amjadi ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Treg Cells

scholarly journals Therapeutic Effect of Exogenous Treg Cells on Collagen-Induced Arthritis and Rheumatoid Arthritis

2019 ◽  
Author(s):  
Shutong Li ◽  
Hongxing Wang ◽  
Hui Wu ◽  
Guoqing Zhang ◽  
Xiaotian Chang
Keyword(s):  
Rheumatoid Arthritis ◽  
Flow Cytometry ◽  
Peripheral Blood ◽  
Synovial Fibroblast ◽  
Treg Cells ◽  
Cell Counting ◽  
Fibroblast Cells ◽  
Collagen Induced Arthritis ◽  
Gm Csf

Abstract Background Regulatory T (Treg) cells have anti-inflammatory and anti-autoimmune functions. The proportion and functions of Treg cells are perturbed in rheumatoid arthritis (RA) patients. Methods Human Treg cells were induced to amplify in vitro and cocultured with RA synovial fibroblast cells (RASFs). The proliferation and apoptosis of RASFs were determined by the cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. Human Treg cells were also injected to collagen-induced arthritis (CIA) rats via the tail vein. Changes in lymphocyte subtypes and cytokines in the peripheral blood and spleen were observed by flow cytometry. Results After coculture with the Treg cells, the proliferation of RA synovial fibroblast cells decreased (p<0.01), and the rate of apoptosis increased (p=0.037). The human Treg cells were injected into the tail veins of collagen-induced arthritis (CIA) rats. The severity of the CIA was reduced (p<0.01) following the injection, the percentages of rat endogenous Treg cells in the peripheral blood and spleen increased significantly (p=0.007 and p<0.01, respectively), and the proportion of B cells decreased (p=0.031). The levels of interleukin IL-5 and IL-6 and the Th1/Th2 ratio in the peripheral blood were significantly decreased (p=0.013, 0.009 and 0.012, respectively). The number of NK cells and the levels of IL-4, IL-13, TNF-α, IFN-γ and GM-CSF in the peripheral blood and spleen did not change significantly. Conclusion These results suggest that exogenous Treg cells play a therapeutic role in RA and CIA. Treg cell treatment could serve as a therapy for RA.

Maresin 1 improves the Treg/Th17 imbalance in rheumatoid arthritis through miR-21

2018 ◽  
Vol 77 (11) ◽  
pp. 1644-1652 ◽  
Author(s):  
Shengwei Jin ◽  
Huaijun Chen ◽  
Yongsheng Li ◽  
Hao Zhong ◽  
Weiwei Sun ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Transcription Factor ◽  
Inverse Correlation ◽  
Joint Inflammation ◽  
Clinical Score ◽  
Treg Cells ◽  
Maresin 1 ◽  
Inflammation Resolution ◽  
Microarray Studies ◽  
Microrna Microarray

ObjectiveTreg/Th17 imbalance plays an important role in rheumatoid arthritis (RA). Maresin 1 (MaR1) prompts inflammation resolution and regulates immune responses. We explored the effect of MaR1 on RA progression and investigated the correlation between MaR1 and Treg/Th17 balance.MethodsBoth patients with RA and healthy controls were recruited into the study. Collagen-induced arthritis (CIA) model was constructed to detect the clinical score, histopathological changes and Treg/Th17 ratio. Purified naive CD4+ T-cells were used to study the effect of MaR1 on its differentiation process and microRNA microarray studies were performed to investigate MaR1 downstream microRNAs in this process. MicroRNA transfection experiments were conducted by lentivirus to verify the mechanism of MaR1 on Treg/Th17 balance.ResultsCompared with controls, the MaR1 concentration was higher in the patients with inactive RA and lower in the patients with active RA. Expression of the Treg transcription factor FoxP3 was the highest in inactive RA and the lowest in active RA, while the Th17 transcription factor RORc showed a reverse trend. An inverse correlation was observed between the FoxP3/RORc ratio and Disease Activity Score 28. Intervention of MaR1 in the CIA model reduced joint inflammation and damage, and improved the imbalanced Treg/Th17 ratio. MaR1 increased Treg cells proportion while reduced Th17 cells proportion under specific differentiation conditions. Furthermore, miR-21 was verified as MaR1 downstream microRNA, which was upregulated by MaR1, modulating the Treg/Th17 balance and thus ameliorating the RA progression.ConclusionsMaR1 is a therapeutic target for RA, likely operating through effects on the imbalanced Treg/Th17 ratio found in the disease.

scholarly journals Editorial: Quality or quantity? Unraveling the role of Treg cells in rheumatoid arthritis

2013 ◽  
Vol 65 (3) ◽  
pp. 552-554 ◽  
Author(s):  
Berent Prakken ◽  
Ellen Wehrens ◽  
Femke van Wijk
Keyword(s):  
Rheumatoid Arthritis ◽  
Treg Cells

scholarly journals Mesenchymal Stem Cells from Patients with Rheumatoid Arthritis Display Impaired Function in Inhibiting Th17 Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Yue Sun ◽  
Wei Deng ◽  
Linyu Geng ◽  
Lu Zhang ◽  
Rui Liu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Th17 Cell ◽  
Mononuclear Cells ◽  
Biological Activities ◽  
Treg Cells ◽  
Cell Polarization ◽  
Peripheral Blood Mononuclear ◽  
Tfh Cells

Mesenchymal stem cells (MSCs) possess multipotent and immunomodulatory properties and are suggested to be involved in the pathogenesis of immune-related diseases. This study explored the function of bone marrow MSCs from rheumatoid arthritis (RA) patients, focusing on immunomodulatory effects. RA MSCs showed decreased proliferative activity and aberrant migration capacity. No significant differences were observed in cytokine profiles between RA and control MSCs. The effects of RA MSCs on proliferation of peripheral blood mononuclear cells (PBMCs) and distribution of specific CD4+T cell subtypes (Th17, Treg, and Tfh cells) were investigated. RA MSCs appeared to be indistinguishable from controls in suppressing PBMC proliferation, decreasing the proportion of Tfh cells, and inducing the polarization of Treg cells. However, the capacity to inhibit Th17 cell polarization was impaired in RA MSCs, which was related to the low expression of CCL2 in RA MSCs after coculture with CD4+T cells. These findings indicated that RA MSCs display defects in several important biological activities, especially the capacity to inhibit Th17 cell polarization. These functionally impaired MSCs may contribute to the development of RA disease.

scholarly journals B cell depletion treatment decreases Th17 cells in patients with rheumatoid arthritis

2021 ◽  
Author(s):  
Constantina A. Bounia ◽  
Stamatis-Nick C Liossis
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
B Cell ◽  
Th17 Cell ◽  
Th17 Cells ◽  
Treg Cells ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Das28 Score ◽  
Autoimmune Rheumatic Diseases

Abstract Introduction: We aimed to evaluate for any possible effects of treatment with rituximab (RTX) on the peripheral Th17 and Treg subpopulations in patients with rheumatoid arthritis (RA).Patients and methods: We analyzed 16 patients with RA initiating RTX treatment, 11 patients with RA initiating abatacept treatment, 11 patients with RA treated with other medications, 8 patients with other autoimmune rheumatic diseases initiating RTX, and 14 healthy volunteers. Th17 cells (CD4+IL23R+IL17A+) and Treg cells (CD4+CD25hiFoxP3+) were evaluated flow-cytometrically.Results: Th17 cells from patients treated with RTX decreased significantly at weeks 8 and 16 (mean ± SEΜ: 3.01% ± 0.54℅ CD4+ cells at week 0 vs. 1.53% ± 0.24℅ at week 8 vs 1.10% ± 0.20℅ at week 16, p = 0.0004). Reductions of Th17 cells were evident in:clinical responders (DAS28 score ≤ 3.2), ACPA (+) and RF (-) patients; circulating Tregs remained stable. Th17 and Tregs were not affected by ABA treatment or by changes in disease activity. Tregs, but not Th17 cells, decreased following treatment with RTX in patients with other autoimmune diseases (0.75% ± 0.16% at week 0 vs. 0.43% ± 0.16% at week 8, p = 0.033).Conclusion: RTX-induced B cell depletion results in a significant reduction of circulating Th17 cell percentages, whereas it has no effect on Tregs of patients with RA. This reduction of Th17 cells was evident particularly in responders to RTX treatment, ACPA+ and RF (-) patients with RA.

scholarly journals Function and Role of Regulatory T Cells in Rheumatoid Arthritis

2021 ◽  
Vol 12 ◽  
Author(s):  
Qi Jiang ◽  
Guocan Yang ◽  
Qi Liu ◽  
Shengjun Wang ◽  
Dawei Cui
Keyword(s):  
Rheumatoid Arthritis ◽  
Autoimmune Diseases ◽  
Tissue Injury ◽  
Treg Cells ◽  
Self Tolerance ◽  
Progression Of Disease ◽  
Loss Of Tolerance ◽  
Vital Component ◽  
The Ideal

Rheumatoid arthritis (RA) is a systemic and heterogeneous autoimmune disease with symmetrical polyarthritis as its critical clinical manifestation. The basic cause of autoimmune diseases is the loss of tolerance to self or harmless antigens. The loss or functional deficiency of key immune cells, regulatory T (Treg) cells, has been confirmed in human autoimmune diseases. The pathogenesis of RA is complex, and the dysfunction of Tregs is one of the proposed mechanisms underlying the breakdown of self-tolerance leading to the progression of RA. Treg cells are a vital component of peripheral immune tolerance, and the transcription factor Foxp3 plays a major immunosuppressive role. Clinical treatment for RA mainly utilizes drugs to alleviate the progression of disease and relieve disease activity, and the ideal treatment strategy should be to re-induce self-tolerance before obvious tissue injury. Treg cells are one of the ideal options. This review will introduce the classification, mechanism of action, and characteristics of Treg cells in RA, which provides insights into clinical RA treatment.

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