Autoimmune diseases, including arthritis, often result from an imbalance between regulatory T (Treg) cells and IL-17-producing (Th17) cells. Dozens of studies in mice and humans have shed light on the pathological significance of T cells in RA. Since Th17 cells play an important role in the exacerbation of inflammation and bone destruction in joints, it has been an important issue how arthritic Th17 cells arise. Th17 cells are generated in the local inflammatory milieu via cytokines produced by macrophages or synovial fibroblasts, while it is reported that Th17 cells are generated in the gut in the presence of specific commensal bacteria. A recent report showed a pathogenic Th17 cell subset with a distinct pattern of gene expression and a potent osteoclastogenic ability are converted from Foxp3⁺ T cells in arthritic joints. Since Foxp3⁺ Treg cells contain T cells which recognize self-antigens, the fate of plastic Foxp3⁺ T cells can be a critical determinant of autoimmunity or self-tolerance. Further analysis on the molecular basis and antigen-specificity of arthritogenic Th17 cell subsets will be helpful to establish novel therapeutic approaches and clarify how self-tolerance breaks down in autoimmune arthritis.