Sha Yonggang, Markovic-Plese Silva
Department of Neurology, University of North Carolina at Chapel Hill , Chapel Hill, NC , USA.
Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Front Immunol. 2016 Nov 29;7:543. doi: 10.3389/fimmu.2016.00543. eCollection 2016.
IL-1β plays a crucial role in the differentiation of human Th17 cells. We report here that IL-1RI expression is significantly increased in both naive and memory CD4 T cells derived from relapsing-remitting multiple sclerosis (RR MS) patients in comparison to healthy controls. Interleukin 1 receptor (IL-1R)I expression is upregulated in the -differentiated Th17 cells from RR MS patients in comparison to the Th1 and Th2 cell subsets, indicating the role of IL-1R signaling in the Th17 cell differentiation in RR MS. When IL-1RI gene expression was silenced using siRNA, human naive CD4 T cells cultured in the presence of Th17-polarizing cytokines had a significantly decreased expression of interleukin regulatory factor 4 (IRF4), RORc, IL-17A, IL-17F, IL-21, IL-22, and IL-23R genes, confirming that IL-1RI signaling induces Th17 cell differentiation. Since IL-1R gene expression silencing inhibited IRF4 expression and Th17 differentiation, and IRF4 gene expression silencing inhibited Th17 cell differentiation, our results indicate that IL-1RI induces human Th17 cell differentiation in an IRF4-dependant manner. Our study has identified that IL-1RI-mediated signaling pathway is constitutively activated, leading to an increased Th17 cell differentiation in IRF4-dependent manner in patients with RR MS.
白细胞介素-1β（IL-1β）在人类辅助性T细胞17（Th17）细胞的分化过程中发挥着关键作用。我们在此报告，与健康对照相比，复发缓解型多发性硬化症（RR MS）患者来源的初始和记忆性CD4 T细胞中白细胞介素1受体I型（IL-1RI）的表达均显著增加。与Th1和Th2细胞亚群相比，RR MS患者分化的Th17细胞中白细胞介素1受体（IL-1R）I的表达上调，表明IL-1R信号在RR MS患者的Th17细胞分化中发挥作用。当使用小干扰RNA（siRNA）使IL-1RI基因表达沉默时，在Th17极化细胞因子存在的情况下培养的人类初始CD4 T细胞中，白细胞介素调节因子4（IRF4）、维甲酸相关孤儿受体c（RORc）、IL-17A、IL-17F、IL-21、IL-22和IL-23R基因的表达显著降低，证实IL-1RI信号诱导Th17细胞分化。由于IL-1R基因表达沉默抑制了IRF4表达和Th17分化，而IRF4基因表达沉默也抑制了Th17细胞分化，我们的结果表明IL-1RI以IRF4依赖的方式诱导人类Th17细胞分化。我们的研究发现，IL-1RI介导的信号通路持续激活，导致RR MS患者以IRF4依赖的方式增加Th17细胞分化。
