A study published in *Nature Medicine* (2014) reveals that Foxp3⁺ regulatory T cells can convert into pathogenic Th17 cells in autoimmune arthritis, contributing to disease progression. The research shows that under arthritic conditions, CD25⁻ Foxp3⁺ CD4⁺ T cells lose Foxp3 expression and differentiate into Th17 cells, which are more potent in promoting osteoclastogenesis and joint destruction. These exFoxp3 Th17 cells express markers like CCR6, CCL20, and RANKL, and are associated with increased arthritis severity. Synovial fibroblasts, particularly those expressing IL-6, promote this conversion by signaling pathways that drive Th17 differentiation. ExFoxp3 Th17 cells are more aggressive in bone destruction than naive Th17 cells and are characterized by high expression of Sox4, a transcription factor that enhances their survival and function. The study also highlights that autoreactive CD25⁻ Foxp3⁺ T cells, which lose Foxp3 upon activation, play a key role in driving arthritis. These findings suggest that the instability of Foxp3 in regulatory T cells can lead to the generation of pathogenic Th17 cells, contributing to autoimmune diseases like rheumatoid arthritis. The research underscores the importance of understanding the plasticity of Foxp3⁺ T cells in maintaining immune tolerance and preventing autoimmunity.A study published in *Nature Medicine* (2014) reveals that Foxp3⁺ regulatory T cells can convert into pathogenic Th17 cells in autoimmune arthritis, contributing to disease progression. The research shows that under arthritic conditions, CD25⁻ Foxp3⁺ CD4⁺ T cells lose Foxp3 expression and differentiate into Th17 cells, which are more potent in promoting osteoclastogenesis and joint destruction. These exFoxp3 Th17 cells express markers like CCR6, CCL20, and RANKL, and are associated with increased arthritis severity. Synovial fibroblasts, particularly those expressing IL-6, promote this conversion by signaling pathways that drive Th17 differentiation. ExFoxp3 Th17 cells are more aggressive in bone destruction than naive Th17 cells and are characterized by high expression of Sox4, a transcription factor that enhances their survival and function. The study also highlights that autoreactive CD25⁻ Foxp3⁺ T cells, which lose Foxp3 upon activation, play a key role in driving arthritis. These findings suggest that the instability of Foxp3 in regulatory T cells can lead to the generation of pathogenic Th17 cells, contributing to autoimmune diseases like rheumatoid arthritis. The research underscores the importance of understanding the plasticity of Foxp3⁺ T cells in maintaining immune tolerance and preventing autoimmunity.