J Clin Invest. 2024 Nov 1;134(21):e185421. doi: 10.1172/JCI185421.
Endometriosis, characterized by the presence of endometrial-like tissue outside the uterus, is a condition associated with pain and infertility. In this issue of the JCI, Lv et al. illuminate the critical pathophysiological role of the ten-eleven translocation 3 (TET3) in endometriosis. TET3 expression levels were higher in macrophages of endometriotic lesions compared with control endometrial tissue, implicating TET3 as a contributing factor in the chronic inflammation that occurs in endometriosis. TGF-β1 and MCP1 are present in the peritoneal cavity of women with endometriosis, and macrophage exposure to these factors resulted in upregulation of TET3, thereby promoting their survival. Notably, Bobcat339, a selective TET inhibitor, induced apoptosis in these macrophages. Further, myeloid-specific TET3 loss reduced endometriosis in mice. RNA-Seq analysis following TET3 knockdown revealed alterations in cytokine signaling and cell-death pathways, underscoring the therapeutic potential of targeting TET3 in macrophages as a strategy for managing endometriosis.
子宫内膜异位症的特征是子宫内膜样组织出现在子宫外，与疼痛和不孕有关。在本期 JCI 中，Lv 等人阐明了十号染色体缺失的磷酸酶-张力蛋白同源物 3（TET3）在子宫内膜异位症中的关键病理生理作用。与对照子宫内膜组织相比，子宫内膜异位症病变中的巨噬细胞中 TET3 的表达水平更高，这表明 TET3 是子宫内膜异位症中发生的慢性炎症的一个促成因素。转化生长因子-β1 和单核细胞趋化蛋白 1 存在于子宫内膜异位症女性的腹腔中，巨噬细胞暴露于这些因子会导致 TET3 的上调，从而促进其存活。值得注意的是，Bobcat339，一种选择性 TET 抑制剂，可诱导这些巨噬细胞凋亡。此外，髓系特异性 TET3 缺失可减少小鼠的子宫内膜异位症。TET3 敲低后的 RNA-Seq 分析显示细胞因子信号和细胞死亡途径发生改变，强调了靶向巨噬细胞 TET3 作为治疗子宫内膜异位症的一种策略的治疗潜力。
