Transcription factor EB (TFEB), a master lysosomal biogenesis and autophagy regulator, is crucial for cellular homeostasis, and its abnormality is related to diverse inflammatory diseases. Genetic variations in autophagic genes are associated with susceptibility to inflammatory bowel disease (IBD); however, little is known about the role and mechanism of TFEB in disease pathogenesis. In this study, we found that the genetic deletion of TFEB in mouse intestinal epithelial cells (IEC) caused intestinal barrier dysfunction, leading to increased susceptibility to experimental colitis. Mechanistically, TFEB functionally protected IEC in part through peroxisome proliferator-activated receptor gamma coactivator 1alpha (TFEB-PGC1α axis) induction, which consequently suppressed reactive oxygen species. TFEB can directly regulate PGC-1α transcription to control antioxidation level. Notably, TFEB expression is impaired and downregulated in the colon tissues of IBD patients. Collectively, our results indicate that intestinal TFEB participates in oxidative stress regulation and attenuates IBD progression.

中文翻译：

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转录因子EB调节肠上皮细胞活性氧的稳态以减轻炎症性肠病

转录因子EB（TFEB）是溶酶体生物发生和自噬的主要调节因子，对于细胞稳态至关重要，其异常与多种炎症性疾病有关。自噬基因的遗传变异与炎症性肠病（IBD）的易感性相关；然而，人们对TFEB在疾病发病机制中的作用和机制知之甚少。在这项研究中，我们发现小鼠肠上皮细胞（IEC）中TFEB的基因缺失导致肠道屏障功能障碍，导致实验性结肠炎的易感性增加。从机制上讲，TFEB 部分通过过氧化物酶体增殖物激活受体 γ 共激活剂 1α（TFEB-PGC1α 轴）诱导来功能性保护 IEC，从而抑制活性氧。TFEB可以直接调节PGC-1α转录来控制抗氧化水平。值得注意的是，IBD 患者的结肠组织中 TFEB 表达受损并下调。总的来说，我们的结果表明肠道 TFEB 参与氧化应激调节并减弱 IBD 进展。