巨噬细胞的颗粒摄取触发了不同的转录途径，不同地调节炎症和溶酶体基因表达，这一成果由加州大学Christopher K. Glass课题组经过不懈努力而取得。该研究于2025年3月20日发表于国际一流学术期刊《免疫学》杂志上。

课题组研究了巨噬细胞对尿酸钠晶体、焦磷酸钙晶体、铝盐和二氧化硅纳米颗粒的反应。虽然每个颗粒诱导了不同的基因表达模式，但小组发现了一个共同的炎症特征和溶酶体酸化基因的急性激活。使用尿酸钠晶体作为模型，课题组研究人员证明了这种溶酶体基因程序受5 ' -引物AMP激活的蛋白激酶（AMPK）依赖的转录网络调控，包括TFEB， TFE3和表观遗传调节剂DNA甲基转移酶3a （DNMT3A）和DOT1L。这种溶酶体酸化程序与JNK-AP-1依赖性网络并行运行，但在很大程度上独立于驱动晶体诱导的趋化因子和细胞因子表达。这些发现揭示了控制炎症和溶酶体反应的途径的分支，为治疗颗粒相关疾病提供了见解。

研究人员表示，接触颗粒是几种炎症性疾病的驱动因素。

附：英文原文

Title: Particle uptake by macrophages triggers bifurcated transcriptional pathways that differentially regulate inflammation and lysosomal gene expression

Author: Isidoro Cobo, Jessica Murillo, Mohnish Alishala, Stephen Calderon, Roxana Coras, Benjamin Hemming, Faith Inkum, Fiorella Rosas, Riku Takei, Nathan Spann, Thomas A. Prohaska, Paulo V.G. Alabarse, Se-Jin Jeong, Christian K. Nickl, Anyan Cheng, Benjamin Li, Andrea Vogel, Thomas Weichhart, José J. Fuster, Thomas Le, Tara R. Bradstreet, Ashlee M. Webber, Brian T. Edelson, Babak Razani, Benjamin L. Ebert, Reshma Taneja, Robert Terkeltaub, Ru Liu Bryan, Monica Guma, Christopher K. Glass

Issue&Volume: 2025-03-20

Abstract: Exposure to particles is a driver of several inflammatory diseases. Here, we investigated macrophage responses to monosodium urate crystals, calcium pyrophosphate crystals, aluminum salts, and silica nanoparticles. While each particle induced a distinct gene expression pattern, we identified a common inflammatory signature and acute activation of lysosomal acidification genes. Using monosodium urate crystals as a model, we demonstrated that this lysosomal gene program is regulated by a 5′-prime-AMP-activated protein kinase (AMPK)-dependent transcriptional network, including TFEB, TFE3, and the epigenetic regulators DNA methyl transferase 3a (DNMT3A) and DOT1L. This lysosomal acidification program operates in parallel with, but largely independently of, a JNK-AP-1-dependent network driving crystal-induced chemokine and cytokine expression. These findings reveal a bifurcation in pathways governing inflammatory and lysosomal responses, offering insights for treating particle-associated diseases.

DOI: 10.1016/j.immuni.2025.02.023

Source: https://www.cell.com/immunity/abstract/S1074-7613(25)00090-1