Institute of Molecular Medicine, The Feinstein Institute for Medical Research, Manhasset, NY, United States.
Department of Biomedical Science, Graduate School of Biomedical Sciences and Engineering, Hanyang University, Seoul, South Korea.
Front Immunol. 2020 Jul 10;11:1436. doi: 10.3389/fimmu.2020.01436. eCollection 2020.
Proper expression of the transcription factor, Positive regulatory domain 1 (), is required for maintaining homeostasis of human monocyte derived-dendritic cells (MO-DCs). The molecular mechanisms and gene targets of PRDM1 in B and T lymphocytes have been identified. However, the function of PRDM1 in dendritic cells (DCs) remains unclear. We investigate co-regulators of PRDM1 in MO-DCs identified by mass spectrometry (MS) and co-immunoprecipitation (Co-IP). Notably, non-POU domain-containing octamer-binding protein (NonO) was found to be a PRDM1 binding protein in the nucleus of MO-DCs. NonO is recruited to the PRDM1 binding site in the promoter region of IL-6. Knockdown of NonO expression by siRNA lessened suppression of IL-6 promoter activity by PRMD1 following LPS stimulation. While NonO binding to PRDM1 was observed in human myeloma cell lines, an effect of NonO on IL-6 expression was not observed. Thus, loss of NonO interrupted the inhibitory effect of PRDM1 on IL-6 expression in MO-DCs, but not plasma cells. Moreover, MO-DCs with low expression of PRDM1 or NonO induce an increased number of IL-21-producing T-like cells . These data suggest that low level of PRDM1 and NonO lead to enhanced activation of MO-DCs and the regulation of MO-DC function by PRDM1 is mediated through cell lineage-specific mechanisms.
转录因子阳性调控域 1 () 的正确表达对于维持人单核细胞衍生树突状细胞 (MO-DC) 的内稳态是必需的。已经鉴定了 PRDM1 在 B 和 T 淋巴细胞中的分子机制和基因靶标。然而，PRDM1 在树突状细胞 (DC) 中的功能尚不清楚。我们通过质谱 (MS) 和共免疫沉淀 (Co-IP) 研究了 MO-DC 中 PRDM1 的共调节因子。值得注意的是，非 POU 结构域包含八聚体结合蛋白 (NonO) 被发现是非 MO-DC 细胞核中 PRDM1 的结合蛋白。NonO 被募集到 IL-6 启动子区域的 PRDM1 结合位点。用 siRNA 敲低 NonO 表达可减轻 LPS 刺激后 PRMD1 对 IL-6 启动子活性的抑制作用。虽然在人骨髓瘤细胞系中观察到 NonO 与 PRDM1 的结合，但未观察到 NonO 对 IL-6 表达的影响。因此，NonO 的缺失中断了 PRDM1 对 MO-DC 中 IL-6 表达的抑制作用，但对浆细胞没有影响。此外，PRDM1 或 NonO 低表达的 MO-DC 诱导产生更多数量的 IL-21 产生 T 样细胞。这些数据表明，PRDM1 和 NonO 的低水平导致 MO-DC 的激活增强，PRDM1 对 MO-DC 功能的调节是通过细胞谱系特异性机制介导的。
