Liu Wei, Sheng Shuman, Zhu Chendi, Li Changzhong, Zou Yonghui, Yang Chunrun, Chen Zi-Jiang, Wang Fei, Jiao Xue
Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Shandong University, Jinan, China; Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Affiliated to Shandong First Medical University, Jinan, China.
Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Affiliated to Shandong First Medical University, Jinan, China.
Mucosal Immunol. 2023 Apr;16(2):121-134. doi: 10.1016/j.mucimm.2023.02.003. Epub 2023 Feb 23.
Immune dysregulation has long been proposed to be associated with adenomyosis, but the underlying mediators and mechanisms remain largely unexplored. Here, we used flow cytometry to investigate the alterations in immune cell subsets in adenomyotic uteri and analyze the phenotype and function of abnormal immune cells. We found that an increase in cluster of differentiation (CD)8 T-cell number was the predominant alteration in ectopic lesions in patients with adenomyosis and was significantly associated with the severity of adenomyosis. Importantly, we identified an exhausted natural killer group protein 2A (NKG2A)CD8 T-cell subset that was associated with the severity of adenomyosis and found that the number of these cells was significantly increased in the eutopic endometrium and ectopic lesions. In addition, the increases in the expression of NKG2A ligand histocompatibility leucocyte antigen E and interleukin-15 in glandular epithelial cells in the adenomyotic microenvironment might contribute to CD8 T-cell exhaustion by promoting NKG2A expression on CD8 T cells or inhibiting the effector function of these cells. In conclusion, our data revealed a previously unrecognized role for NKG2ACD8 T-cell exhaustion in the pathogenesis of adenomyosis, indicating that therapeutic interventions designed to target and reinvigorate exhausted CD8 T cells may be beneficial for patients with adenomyosis.
长期以来，人们一直认为免疫失调与子宫腺肌病有关，但潜在的介质和机制在很大程度上仍未得到探索。在此，我们使用流式细胞术研究子宫腺肌病患者子宫中免疫细胞亚群的变化，并分析异常免疫细胞的表型和功能。我们发现，分化簇（CD）8 T细胞数量增加是子宫腺肌病患者异位病灶中的主要变化，并且与子宫腺肌病的严重程度显著相关。重要的是，我们鉴定出一种耗竭的自然杀伤细胞组蛋白2A（NKG2A）CD8 T细胞亚群，其与子宫腺肌病的严重程度相关，并发现这些细胞的数量在在位子宫内膜和异位病灶中显著增加。此外，子宫腺肌病微环境中腺上皮细胞中NKG2A配体组织相容性白细胞抗原E和白细胞介素-15表达的增加可能通过促进CD8 T细胞上NKG2A的表达或抑制这些细胞的效应功能而导致CD8 T细胞耗竭。总之，我们的数据揭示了NKG2A+CD8 T细胞耗竭在子宫腺肌病发病机制中以前未被认识的作用，表明旨在靶向并恢复耗竭的CD8 T细胞活力的治疗干预措施可能对子宫腺肌病患者有益。
