Induction of the IL-1RII decoy receptor by NFAT/FOXP3 blocks IL-1β-dependent response of Th17 cells.
Induction of the IL-1RII decoy receptor by NFAT/FOXP3 blocks IL-1β-dependent response of Th17 cells.
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NFAT/FOXP3诱导IL-1RII诱骗受体阻断Th17细胞il -1β依赖性应答。
作者：
Kim DH;Kim HY;Cho S;Yoo SJ;Kim WJ;Yeon HR;Choi K;Choi JM;Kang SW;Lee WW
Th17和Treg细胞来自共同的前体细胞，必须在免疫系统内保持平衡，以预防自身免疫性疾病。IL-1β介导的IL-1受体(IL-1R)信号转导对Th17细胞生物学至关重要。IL-1R信号的微调由IL-1RI和IL-RII两种受体、IL-1R辅助蛋白和IL-1R拮抗剂控制。我们证明，诱骗受体IL-1RII通过限制IL-1β的反应性，在TCR刺激的表达功能性IL-1RI的CD_4+T细胞中调节IL-17的反应。NFAT通过与Foxp3的相互作用调节IL-1RII的表达。NFAT/FOXP3复合体与IL-1RII启动子结合，对其转录起关键作用。此外，类风湿关节炎患者的CD4+T细胞中IL-1RII表达异常。因此，IL-1RS在活化的CD4+T细胞上的差异表达确定了独特的免疫学特征，并为IL-1RII的表达奠定了新的分子机制。这些发现揭示了IL-1RII对Th17反应的调节作用。
Derived from a common precursor cell, the balance between Th17 and Treg cells must be maintained within immune system to prevent autoimmune diseases. IL-1β-mediated IL-1 receptor (IL-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 decoy receptor, IL-1RII, is important for regulating IL-17 responses in TCR-stimulated CD4+ T cells expressing functional IL-1RI via limiting IL-1β responsiveness. IL-1RII 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 IL-1RII on Th17 responses.