Th17 Transcription Factor RORC2 Is Inversely Correlated with FOXP3 Expression in the Joints of Children with Juvenile Idiopathic Arthritis

Abstract

We demonstrated for the first time an increased synovial expression of the transcription factor of Th17, RORC2, in JIA, and its inverse relationship with FOXP3 mRNA. These results extend research on "Th17" and Tregs in JIA.

Evidence of the transient nature of the Th17 phenotype of CD4+CD161+ T cells in the synovial fluid of patients with juvenile idiopathic arthritis

“…These findings are partially in agreement with the results reported in other investigations (22)(23)(24), in which increased levels of IL-17A, IL-17A-producing cells, and RORC have been demonstrated in the SF of children with JIA. In addition, we also observed an enrichment for CD4ϩCD161ϩ T cells in the JIA SF, the majority of which exhibited either the Th17/Th1 phenotype or the nonclassic Th1 (RORCϩIFN␥ϩIL-17Ϫ) phenotype.…”

“…T cell infiltrates predominantly consist of Th1-skewed cells, which were thought to have a central role in disease pathogenesis (21). After the association between Th17 cells and several human autoimmune diseases, including RA, was observed, some studies found increased levels of IL-17A, as well as the presence of Th17 cells and the expression of their transcription factor, RORC, in the synovial fluid (SF) of children with JIA (22)(23)(24)(25)(26).…”

Comparison of Blood and Synovial Fluid Th17 and Novel Peptidase Inhibitor 16 Treg Cell Subsets in Juvenile Idiopathic Arthritis

“…Previous studies have shown that IL-17-producing cells are enriched in the synovial fluid of children with extended oligoarthritis compared with patients with persistent oligoarthritis in a reciprocal relationship with regulatory T cells (Treg) [8]. An inverse relationship between the increased synovial expression of the Th17 transcription factor RORC2 and the Treg transcription factor FOXP3 has also been demonstrated in joints of children with JIA [12].…”

T regulatory cells in childhood arthritis – novel insights

“…2). Interestingly, Treg in the blood of children with O-JIA appear to be present at normal or even decreased frequency, compared with healthy children (Refs 3, 79,80). In an early study of the very severe form of JIA known as systemic JIA (sJIA; a form of disease where in addition to arthritis, patients display systemic symptoms such as fever, rash and major organ involvement), Treg were shown to be reduced in peripheral blood in severe active disease, just before autologous stem cell transplantation.…”