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Th17 transcription factor rorc2 is inversely correlated with FOXP3 expression in the joints of children with juvenile idiopathic arthritis
Journal of Rheumatology, 09/09/09
Olivito B et al. – There is an increased synovial expression of the transcription factor of Th17, RORC2, in JIA, and its inverse relationship with FOXP3 mRNA.
Methods- 65 children with JIA (18 males and 47 females; median age, 6.2 yrs; 45 with oligoarticular and 20 with polyarticular ds) and 75 age- and gender-matched healthy controls were studied
- Flow cytometry was used to analyze the forkhead box P3 (FOXP3)-positive Treg cells in peripheral blood and synovial fluid mononuclear cells
- FOXP3 and retinoic-acid related orphan receptor C isoform 2 (RORC2) mRNA were assessed by real-time polymerase chain reaction analysis
- Cytokines (IL-17 and Th1/Th2 related cytokines) were measured in culture supernatants of 11 paired PBMC and SFMC activated with PMA and ionomycin
- FOXP3+ T cells and FOXP3 mRNA amounts were significantly lower in PB of children with JIA as compared with controls and a higher percentage of Treg cells with concomitant higher level of FOXP3 transcript levels were observed in SF when compared with their PB counterparts
- SF CD4+FOXP3+ T cells were characterized by higher amounts of FOXP3 protein per cell when compared with peripheral CD4+FOXP3+ T cells, as revealed by the difference in FOXP3 median fluorescence intensity (median ± SD, arbitrary units, 54 ± 22.6 vs 19.5 ± 4.2)
- RORC2 transcript levels were higher in JIA joints when compared with matched PB samples (median fold increase 3.9) but negatively correlated with FOXP3 mRNA levels (r = ?0.623)
- Stimulated SFMC displayed an impaired ability to produce IL-17 when compared with PBMC and, interestingly, an inverse relationship between IL-17 levels and the percentage of CD4+CD25+FOXP3+ SF T cells (r = ?0.510) was seen
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