Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, China.
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China.
Int Immunopharmacol. 2024 Mar 30;130:111711. doi: 10.1016/j.intimp.2024.111711. Epub 2024 Feb 29.
Immune dysregulation has been summarized as a critical factor in the occurrence and development of Polycystic ovary syndrome (PCOS), but potential mediators and mechanisms remain unclear. Our previous study showed that CD19 B cells were involved in the pathogenesis of dehydroepiandrosterone (DHEA)-induced PCOS mice. Here, we studied the therapeutic potential of anti-CD19 antibody (aCD19 Ab) on DHEA-induced PCOS mice. The results showed that aCD19 Ab treatment improved ovarian pathological structure and function of PCOS mice, manifested by an increased number of corpus luteum, a decreased number of cystic follicles and atretic follicles, and regular estrus cycles. The aCD19 Ab treatment reduced the proportion of splenic CD21 CD23 marginal zone B cells as well as the level of serum IgM and decreased the percentage of peripheral blood and splenic neutrophils. In particular, aCD19 Ab treatment reduced the apoptosis of granulosa cells and macrophage infiltration in ovarian secondary follicles of PCOS mice, as well as the expression of TNF-α in ovarian tissue and serum TNF-α levels. Moreover, we confirmed that TNF-α induced the apoptosis of human ovarian granulosa tumor cell line cells in vitro. Thus, our work demonstrates that aCD19 Ab treatment improves ovarian pathological phenotype and function by reducing local and systemic inflammation in PCOS mice, which may provide a novel insight into PCOS therapy.
免疫失调已被总结为多囊卵巢综合征 (PCOS) 发生和发展的一个关键因素，但潜在的介质和机制仍不清楚。我们之前的研究表明，CD19 B 细胞参与了脱氢表雄酮 (DHEA) 诱导的 PCOS 小鼠的发病机制。在这里，我们研究了抗 CD19 抗体 (aCD19 Ab) 对 DHEA 诱导的 PCOS 小鼠的治疗潜力。结果表明，aCD19 Ab 治疗改善了 PCOS 小鼠的卵巢病理结构和功能，表现为黄体数量增加、囊状卵泡和闭锁卵泡数量减少以及发情周期规律。aCD19 Ab 治疗降低了脾 CD21 CD23 边缘带 B 细胞的比例以及血清 IgM 水平，并降低了外周血和脾中性粒细胞的百分比。特别是，aCD19 Ab 治疗减少了 PCOS 小鼠卵巢次级卵泡中颗粒细胞的凋亡和巨噬细胞浸润，以及卵巢组织和血清 TNF-α 水平中的 TNF-α 表达。此外，我们证实 TNF-α 在体外诱导人卵巢颗粒细胞瘤细胞系细胞凋亡。因此，我们的工作表明，aCD19 Ab 通过减少 PCOS 小鼠局部和全身炎症来改善卵巢病理表型和功能，这可能为 PCOS 治疗提供新的思路。
