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Generation of Induced-pluripotent Stem Cells Using Fibroblast-like Synoviocytes Isolated from Joints of Rheumatoid Arthritis Patients
Published on: October 16, 2016
FoxP3 mRNA splice forms in synovial CD4+ T cells in rheumatoid arthritis and psoriatic arthritis
L Rebekka Ryder1, Else Marie Bartels, Anders Woetmann
1The Parker Institute, Frederiksberg Hospital, Denmark.
Abstract:
Our aim was to elucidate the relative amount of the different splice forms of FoxP3 mRNA in CD4+ T cells in peripheral blood (PB) compared to synovial fluid (SF) in RA and PsA patients. FoxP3 mRNA was measured using a quantitative real-time PCR method. CD4+ T cells were isolated from 17 paired samples of PB and SF from RA and PsA patients, and PB from 10 controls. FoxP3fl and FoxP3Δ2 mRNA was significantly increased (6.7 and 2.1-fold, respectively) in PB CD4+ T cells from RA patients compared to controls. FoxP3fl and Δ2 mRNA in SF CD4+ T cells was increased compared to controls in sero-negative RA and PsA, but not in sero-positive RA patients, who had a high FoxP3 expression in both PB and SF. The FoxP3Δ2Δ7 mRNA was barely detectable in patient samples, and not at all in healthy individuals. We provide evidence of an increased expression of FoxP3 splice forms in synovial CD4+ T cells from RA patients. A skewed, high expression profile of FoxP3, but not CTLA-4, in sero-negative RA and PsA, indicates that synovial CD4+ T cells may represent unique subsets of T cells which have been induced locally or selectively recruited to the joint.
Insights
Researchers studied FoxP3 mRNA splice variants in CD4+ T cells from rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients. Increased FoxP3 mRNA was found in peripheral and synovial fluid, suggesting unique T cell subsets in the joints.
Area of Science:
- Immunology
- Molecular Biology
- Rheumatology
Background:
- Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are inflammatory conditions involving immune system dysregulation.
- Regulatory T cells (Tregs), characterized by FoxP3 expression, play a crucial role in immune homeostasis.
- Understanding FoxP3 splice variants in different disease contexts is essential for elucidating Treg function.
Purpose of the Study:
- To compare the expression levels of distinct FoxP3 mRNA splice forms in CD4+ T cells from peripheral blood (PB) and synovial fluid (SF).
- To investigate these expression patterns in patients with RA and PsA compared to healthy controls.
Main Methods:
- Quantitative real-time PCR was employed to measure FoxP3 mRNA splice variants.
- CD4+ T cells were isolated from paired PB and SF samples of RA and PsA patients, and from PB of healthy controls.
Main Results:
- FoxP3fl and FoxP3Δ2 mRNA levels were significantly elevated in PB CD4+ T cells of RA patients compared to controls.
- SF CD4+ T cells showed increased FoxP3fl and Δ2 mRNA in sero-negative RA and PsA, but not sero-positive RA.
- FoxP3Δ2Δ7 mRNA was minimally detected in patient samples and absent in healthy individuals.
Conclusions:
- Synovial CD4+ T cells in RA patients exhibit increased expression of FoxP3 splice forms.
- A distinct, high FoxP3 expression profile in sero-negative RA and PsA suggests unique, locally induced or recruited synovial T cell subsets.
- These findings highlight potential differences in immune cell populations within the joints of specific patient groups.
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