Induction of the IL-1RII decoy receptor by NFAT/FOXP3 blocks IL-1β-dependent response of Th17 cells

Derived from a common precursor cell, the balance between Th17 and Treg cells must be maintained within immune system to prevent autoimmune diseases. IL-1 beta-mediated IL-1 receptor (1L-1R) signaling is essential for Th17-cell biology. Fine-tuning of IL-1R signaling is controlled by two receptors, IL-1RI and IL-RII, IL-1R accessory protein, and IL-1R antagonist. We demonstrate that the dec oy receptor, IL-1RII, is important for regulating IL-17 responses in TCR-stimulated CD4(+) T cells expressing functional IL-1 RI via limiting IL-1 beta responsiveness. IL-1 RII expression is regulated by NFAT via its interaction with Foxp3. The NFAT/FOXP3 complex binds to the IL-1RII promoter and is critical for its transcription. Additionally, IL-1RII expression is dysregulated in CD4(+) T cells from patients with rheumatoid arthritis. Thus, differential expression of IL-1Rs on activated CD4(+) T cells defines unique immunological features and a novel molecular mechanism underlies IL-1RII expression. These findings shed light on the modulatory effects of IL1RII on Th17 responses.