The aim of this study was to assess the possible association of the functional (GT)(n) microsatellite polymorphism in the FOXP3 gene with predisposition to several autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ulcerative colitis (UC), Crohn's disease, and celiac disease.
This study has shown, for the first time in human RA, the efficacy of autologous Tregs in reducing the inflammatory activity of synovial tissue cell cultures ex vivo, while in the synovium FoxP3+ Tregs of patients with RA are reduced compared with peripheral blood and synovial fluid.
There is an accumulation of FoxP3-expressing regulatory T cells in RA SF, and such recruitment may be dependent on the distinct chemokine receptors expressed on regulatory T cells.
Mutations in Foxp3 are responsible for the scurfy (sf) mutant mouse, and for autoimmune human diseases including the X-linked fatal "immune dysregulation, polyendocrinopathy, enteropathy, X-linked" (IPEX), autoimmune colitis and rheumatoid arthritis.
We observed an increased expression of full-length FoxP3 mRNA in RA patients when compared to healthy controls, as well as an increase in CD25 mRNA expression, but no corresponding increase in CTLA-4 mRNA expression.
RA patients express more full-length FoxP3 than healthy controls in peripheral blood CD4-positive cells, suggesting an increased number of regulatory T cells (Tregs).
Decreased mRNA expression of two FOXP3 isoforms in peripheral blood mononuclear cells from patients with rheumatoid arthritis and systemic lupus erythematosus.
The present study provides the first evidence of increased CD25(-)FOXP3(+) cells in RA patients, which were associated with disease activity and with GC treatment in carriers of the high IL-10 genotype, suggesting that this population plays a role in the clinical response to prednisone in RA.
Frequencies of Foxp3(+) Helios(+) Treg, unlike Foxp3(+) Helios(-) T cells, were significantly increased in SLE patients and positively correlated with disease activity, whereas they were unaltered in SSc and RA patients.
Our aim was to clarify if anti-tumour necrosis factor (TNF) drugs have effect on expression of three splice forms of FoxP3 mRNA in blood CD4+ T cells from rheumatoid arthritis (RA) patients compared with healthy controls.
In this study, we demonstrated that the frequencies of CD3(+) CD4(+) IL-17(+) Th17 cells were significantly higher, and CD4(+) CD25(+) FOXP3(+) Treg cells significantly lower in peripheral blood mononuclear cells from RA patients.
Furthermore, DMR methylation negatively correlated with FOXP3 mRNA expression, and Treg cells isolated from rheumatoid factor negative RA patients were found to express significantly higher levels of FOXP3 than Treg cells from RhF-positive patients, with an associated decrease in DMR methylation.
Despite their reduced suppressive activity, Tregs in the RA joint were highly proliferative and expressed FOXP3, CD39, and CTLA-4, which are markers of functional Tregs.
After appropriate adjustment of Bonferroni correction for multiple testing, the genotype-phenotype analysis showed no significant correlation of the Foxp3-3279 C/A and -924 A/G polymorphisms with the disease activity, joint damage, laboratory variables, and extraarticular manifestation in patients with RA.
CTLA-4 and FoxP3 expression was measured by flow cytometry and quantitative polymerase chain reaction (qPCR) in Treg cells from healthy individuals and RA patients.
In addition, we summarize the role of dendritic cells and Foxp3+ regulatory T cells in both peripheral and thymic tolerance, and highlight their relevance to what we know about the aetiology of RA.
The expression quantitative trait loci (eQTL) analysis revealed a significant gender effect of the FoxP3 promoter polymorphism rs3761548A/C on miR-221, miR-222 and miR-532 expression levels, and of the FoxP3 polymorphism rs2232365A/G on miR-221 expression levels in PBMC of RA patients.
It was observed that in peripheral blood, CD4+CD25-FOXP3+/CD4+ levels were reduced in the RA group (P<0.001), and sPD‑1 levels were markedly higher (P<0.001), compared with the HC group.