FoxP3 mRNA splice forms in synovial CD4+ T cells in rheumatoid arthritis and psoriatic arthritis
Abstract
Ryder LR, Bartels EM, Woetmann A, Madsen HO, Ødum N, Bliddal H, Danneskiold‐Samsøe B, Ribel‐Madsen S, Ryder LP. FoxP3 mRNA splice forms in synovial CD4+ T cells in rheumatoid arthritis and psoriatic arthritis. APMIS 2012; 120: 387–96. 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.Keywords
This publication has 48 references indexed in Scilit:
- Genome-Wide Analysis of Immune Activation in Human T and B Cells Reveals Distinct Classes of Alternatively Spliced GenesPLOS ONE, 2009
- Regulating the regulators: costimulatory signals control the homeostasis and function of regulatory T cellsImmunological Reviews, 2009
- NK-Dependent Increases in CCL22 Secretion Selectively Recruits Regulatory T Cells to the Tumor MicroenvironmentThe Journal of Immunology, 2009
- Defects in CTLA-4 are associated with abnormal regulatory T cell function in rheumatoid arthritisProceedings of the National Academy of Sciences, 2008
- Forced overexpression of either of the two common human Foxp3 isoforms can induce regulatory T cells from CD4+CD25– cellsEuropean Journal of Immunology, 2008
- The quantitative analysis of peripheral blood FOXP3‐expressing T cells in systemic lupus erythematosus and rheumatoid arthritis patientsEuropean Journal of Clinical Investigation, 2007
- Global analysis of alternative splicing during T-cell activationRNA, 2007
- Splice variants of human FOXP3 are functional inhibitors of human CD4+ T‐cell activationImmunology, 2006
- Cytotoxic T lymphocyte antigen‐4‐dependent down‐modulation of costimulatory molecules on dendritic cells in CD4+ CD25+ regulatory T‐cell‐mediated suppressionImmunology, 2006
- The american rheumatism association 1987 revised criteria for the classification of rheumatoid arthritisArthritis & Rheumatism, 1988