Synovial and Peripheral Blood CD4+FoxP3+ T Cells in Spondyloarthritis

Appel, Heiner; Wu, Peng; Scheer, Rebecca; Kedor, Claudia; Sawitzki, Birgit; Thiel, Andreas; Radbruch, Andreas; Sieper, Joachim; Syrbe, Uta

doi:10.3899/jrheum.110377

Cited by 48 publications

(20 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The increased percentages of the Tregs population in our AS patients suggest that an enhanced immuno-regulatory mechanism is present in disease processing. This may result from the existence of a positive feedback system in which the inducible regulatory T cells are generated and triggered due to ongoing inflammation [27,30,31]. It has been shown that the FoxP3 expression can be induced in human CD4 + CD25 − T cells after cell activation [32,33].…”

Section: Discussionmentioning

confidence: 98%

Regulatory T cells in ankylosing spondylitis and the response after adalimumab treatment

et al. 2015

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 98%

Regulatory T cells in ankylosing spondylitis and the response after adalimumab treatment

et al. 2015

View full text Add to dashboard Cite

“…DNA extraction and methylation‐specific real‐time PCR were performed as in Appel et al 2011 and Wieczorek et al, 2009 , using a minimum of 60 ng bisulfite‐treated (EpiTect; Qiagen) genomic DNA. Results are reported as % T cells with demethylated TSDR region.…”

Section: Methodsmentioning

confidence: 99%

Short‐term cytokine stimulation reveals regulatory T cells with down‐regulated Foxp3 expression in human peripheral blood

et al. 2017

Self Cite

View full text Add to dashboard Cite

The identification of regulatory T cells (Treg cells) in human peripheral blood is an important tool in diagnosis, research, and therapeutic intervention. As compared to lymphoid tissues, the frequencies of circulating Treg cells identified as CD4 CD25 Foxp3 are, however, low. We here show that many of these cells remain undetected due to transient down regulation of Foxp3, which rapidly decays in the absence of cytokine-mediated STAT5 signals. Short-term incubation of PBMCs or isolated CD4 T cells, but not of lymph node cells, with IL-2, -7, or -15 more than doubles the frequency of Foxp3 CD25 among CD4 T cells detectable by flow cytometry. This increase is not due to cell division but to upregulation of both proteins. At the same time, the uncovered Treg cells up-regulate CD25 and down-regulate CD127, making them accessible to viable cell sorting. "Latent" Treg cells have a demethylated FOXP3 TSDR sequence, are enriched in naïve, non-cycling cells, and are functional. The confirmation of our findings in RA and SLE patients shows the feasibility of uncovering latent Treg cells for immune monitoring in clinical settings. Finally, our results suggest that unmasking of latent Treg cells contributes to the increase in circulating CD4 CD25 Foxp3 cells reported in IL-2 treated patients.

show abstract

“…Regulatory T cells (Tregs) are a subset of CD4+ CD25high T lymphocytes that require forkhead box transcription factor (FOXP3) for their suppressive function [4, 8, 9]. Tregs derived from the thymus mediate suppression through a contact-dependent mechanism including cytotoxic T-lymphocyte antigen 4 (CTLA-4) [10].…”

Section: Introductionmentioning

confidence: 99%

Abatacept reduces synovial regulatory T-cell expression in patients with psoriatic arthritis

Simonyi

Heffernan

Gogarty³

et al. 2017

Arthritis Res Ther

View full text Add to dashboard Cite

BackgroundThe aim was to study changes in immunohistochemical expression markers of synovial and skin inflammation, clinical outcomes and magnetic resonance imaging (MRI) scores with abatacept treatment in patients with psoriatic arthritis (PsA).MethodsBiological-treatment-naïve PsA patients with active disease including synovitis of a knee were enrolled in this single-centre, crossover study. Patients were randomised to receive intravenous abatacept 3 mg/kg of body weight or placebo infusion on day 1, 15 and 29; thereafter abatacept 10 mg/kg of body weight was administered every 28 days for 5 months. Clinical data were collected at each visit. Synovial biopsy of the involved knee was obtained at baseline and 2 and 6 months. MRI of the same knee and skin biopsy was performed prior to arthroscopy.ResultsFifteen patients were recruited. Significant improvements in the joint-related measures were observed; 90% were European League Against Rheumatism criteria responders and 30% achieved psoriasis area severity index (PASI)50 at 6 months. Reduction in synovitis (P = 0.016) and vascularity (P = 0.039) macroscopic scores consistent with decrease in total MRI score (P = 0.016) were noticed. Abatacept decreased the immunohistological expression of FOXP3+ cells (P = 0.027), specifically the expression of CD4+FOXP3+ regulatory T cells (Tregs) (P = 0.008) in the synovium over 6 months. There was no significant clinical or immunohistological change in any of the skin measures.ConclusionThis is the first study assessing synovial and psoriatic skin immunpathological changes following abatacept treatment in PsA. Reduction in Treg expression in the synovium but not in the psoriatic lesion suggests abnormal Treg function in PsA with differential suppressive capacity in the synovium compared to the lesional skin. The results of this study demonstrate that abatacept 10 mg/kg of body weight might be an effective treatment option for joint disease in patients with PsA.Trial registrationIrish Health Products Regulatory Authority. Trial registration number: CT 900/489/1 – Abatacept (case number: 2077284, EudraCT Number: 2009-017525-19, Protocol number: 77777). Registered on 12 March 2010.

show abstract

Synovial and Peripheral Blood CD4+FoxP3+ T Cells in Spondyloarthritis

Cited by 48 publications

References 23 publications

Regulatory T cells in ankylosing spondylitis and the response after adalimumab treatment

Regulatory T cells in ankylosing spondylitis and the response after adalimumab treatment

Short‐term cytokine stimulation reveals regulatory T cells with down‐regulated Foxp3 expression in human peripheral blood

Abatacept reduces synovial regulatory T-cell expression in patients with psoriatic arthritis

Contact Info

Product

Resources

About