Tet3, also known as ten-eleven translocation methylcytosine dioxygenase 3, is a key enzyme responsible for 5-methylcytosine oxidation and DNA demethylation, playing a vital role in early zygote formation, embryogenesis, and neuronal differentiation [2,5]. It is involved in multiple biological processes such as cell fate commitment, adipogenesis, and immune response regulation [4,6].

In various disease conditions, Tet3 shows distinct impacts. In endometriosis, pathogenic macrophages with Tet3 overexpression promote the disease. Depleting Tet3-overexpressing macrophages via myeloid-specific Tet3 ablation or using Bobcat339 (which triggers Tet3 degradation) inhibits endometriosis progression in mice [1,8]. In pregestational hyperglycemia, reduced Tet3 expression in oocytes leads to glucose intolerance in offspring due to hypermethylation of insulin secretion genes [2]. In rheumatoid arthritis, MIR22 can directly inhibit TET3 translation in fibroblast-like synoviocytes, and Tet3 exerts a pro-inflammatory effect [3]. In white adipose tissue development, selective depletion of Tet3 in adipose precursor cells reduces adipogenesis and protects against diet-induced adipose expansion [4]. In intestinal epithelial cells, Tet3-specific ablation decreases the innate immune response-related transcriptome, making mice more susceptible to enteric pathogen infection and DSS-induced colitis [7].

In conclusion, Tet3 is crucial for normal development and metabolism, and its dysregulation is associated with multiple diseases. Gene knockout mouse models, such as myeloid-specific Tet3 ablation, have significantly contributed to understanding its role in diseases like endometriosis, providing potential therapeutic targets for these conditions.