Department of Human Immunology, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, S1W17, Chuo-ku, Sapporo, 060-8556, Japan.
Department of Human Immunology, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, S1W17, Chuo-ku, Sapporo, 060-8556, Japan.
Biochem Biophys Res Commun. 2019 Jul 5;514(4):1167-1171. doi: 10.1016/j.bbrc.2019.05.057. Epub 2019 May 15.
POU domain class 2-associating factor 1 (also called Bob1), which is mainly expressed in B cells, regulates B cell homeostasis and controls humoral immune responses. Although Bob1 is known to function reliably in T cell subsets including follicular helper T cells, Th1 cells and Th2 cells, it is unknown whether Bob1 functions in other T cell subsets. In this study, we found that Bob1 knock out (KO) mice are resistant to experimental autoimmune encephalomyelitis (EAE) induced by MOG peptide and that Bob1 KO T cells are defective in Th17 differentiation. Importantly, Bob1 interacts with retinoid acid receptor-related orphan receptor (ROR) gamma t (RORγt), a signature transcription factor for Th17 cells, through the ligand-binding domain of RORγt, thereby enhancing IL-17A transcription activity. IL-17A induction by Bob1 requires the ability for its formation of a DNA-Oct1-Bobl ternary complex. Thus, our findings demonstrate that Bob1 enhances IL-17A expression in vivo and in vitro by interacting with RORγt in Th17 cells, suggesting that Bob1 plays a pivotal role in Th17-mediated autoimmune disease.
POU 结构域家族 2 关联因子 1（也称为 Bob1），主要在 B 细胞中表达，调节 B 细胞的内稳态并控制体液免疫反应。尽管 Bob1 已知在包括滤泡辅助 T 细胞、Th1 细胞和 Th2 细胞在内的 T 细胞亚群中可靠地发挥作用，但尚不清楚 Bob1 是否在其他 T 细胞亚群中发挥作用。在这项研究中，我们发现 Bob1 敲除（KO）小鼠对 MOG 肽诱导的实验性自身免疫性脑脊髓炎（EAE）具有抗性，并且 Bob1 KO T 细胞在 Th17 分化中存在缺陷。重要的是，Bob1 通过 RORγt 的配体结合结构域与维甲酸受体相关孤儿受体（ROR）γ t（RORγt）相互作用，RORγt 是 Th17 细胞的特征转录因子，从而增强 IL-17A 的转录活性。Bob1 诱导 IL-17A 的作用需要其形成 DNA-Oct1-Bobl 三元复合物的能力。因此，我们的研究结果表明，Bob1 通过与 Th17 细胞中的 RORγt 相互作用，在体内和体外增强 IL-17A 的表达，表明 Bob1 在 Th17 介导的自身免疫性疾病中发挥关键作用。
