Department of Biological Sciences, Konkuk University, Seoul 05029, Republic of Korea.
Int J Mol Sci. 2023 May 8;24(9):8443. doi: 10.3390/ijms24098443.
Nuclear receptor-binding SET domain-containing protein 1 (NSD1) inactivation in tumor cells contributes to an immune-cold phenotype, indicating its potential association with immune disturbances. NSD is a homolog of the human NSD1. Thus, in this study, we investigated the effect of NSD overexpression in the fat body, the central organ involved in immune responses. Upon ectopic expression of NSD in the fat body, the mRNA levels of antimicrobial peptides increased. Using reporter constructs containing deletions of various NF-κB sites in the Attacin-A () promoter, we found that transcriptional activation by NSD is mainly mediated via the IMD pathway by activating Relish. Since the IMD pathway is required to resist Gram-negative bacterial infections, we further examined the effect of fat body-specific NSD overexpression on immune defenses. Upon oral ingestion of Gram-negative , the survival rate of the NSD-overexpressing larvae was higher than that of the wild type, suggesting a positive role of NSD in immune responses. Taken together, these results suggest the association of NSD with the IMD pathway and is thus expected to contribute to the elucidation of the molecular mechanisms of immune malfunction in various NSD1-associated human diseases.
肿瘤细胞中核受体结合 SET 域蛋白 1（NSD1）的失活导致免疫冷表型，表明其与免疫紊乱有潜在关联。NSD 是人类 NSD1 的同源物。因此，在这项研究中，我们研究了 NSD 在参与免疫反应的中心器官脂肪体中的过表达对其的影响。在脂肪体中异位表达 NSD 后，抗菌肽的 mRNA 水平增加。使用包含 Attacin-A()启动子中各种 NF-κB 位点缺失的报告基因构建体，我们发现 NSD 的转录激活主要通过激活 Relish 经由 IMD 途径介导。由于 IMD 途径是抵抗革兰氏阴性细菌感染所必需的，我们进一步研究了脂肪体特异性 NSD 过表达对免疫防御的影响。当口服革兰氏阴性菌时，过表达 NSD 的幼虫的存活率高于野生型，这表明 NSD 在免疫反应中发挥积极作用。综上所述，这些结果表明 NSD 与 IMD 途径有关，因此有望有助于阐明各种与 NSD1 相关的人类疾病中免疫功能障碍的分子机制。
