MKP1 经抑制支持细胞 IKKβ/NF-κB/IL-6 信号维持睾丸免疫豁免并支持精子生成
MKP1 preserves testicular immune privilege and supports spermiogenesis by suppressing IKKβ/NF-κB/IL-6 signaling in Sertoli cells
摘要
该研究在小鼠中探讨 MAPK 磷酸酶 1（MKP1）在支持细胞（Sertoli 细胞）生理状态下的作用。MKP1 敲除小鼠表现为生育力下降、精子计数减少、精子畸形率升高及精子生成受损；同时血睾屏障完整性受损、睾丸 IL-6 表达升高、血清抗精子抗体增加。机制上，MKP1 与支持细胞 IKKβ 相互作用，抑制 IKKβ/NF-κB 信号及下游 IL-6 表达。用 LMT-28 抑制 IL-6 可挽救 MKP1 缺陷小鼠的精子生成障碍。研究提示 MKP1 通过 IKKβ/NF-κB/IL-6 轴维持睾丸免疫豁免，或可成为炎症性生精障碍的潜在干预靶点。
原文摘要
MAPK phosphatase 1 (MKP1) in Sertoli cells has been shown to protect the blood-testis barrier during LPS-induced inflammation, but its role under physiological conditions is unclear. Here, we show that MKP1 knockout mice exhibit subfertility, reduced sperm counts, increased sperm abnormalities, and impaired spermiogenesis. MKP1 deficiency compromises blood-testis barrier integrity, elevates testicular IL-6 expression, and increases serum anti-sperm antibodies. Mechanistically, MKP1 interacts with IKKβ in Sertoli cells to suppress IKKβ/NF-κB signaling and downstream IL-6 expression. Notably, IL-6 inhibition with LMT-28 rescues the spermatogenic defects in MKP1-deficient mice. Collectively, this study establishes that MKP1 in Sertoli cells maintains testicular immune privilege via the IKKβ/NF-κB/IL-6 axis to support spermiogenesis, offering a potential therapeutic target for inflammatory spermatogenic disorders.
推荐理由：在体基因敲除结合机制解析与 IL-6 抑制挽救实验，链条完整，将支持细胞免疫豁免与生精功能直接联系，对男性不育炎症机制研究有参考价值；但尚属小鼠基础研究，距临床与 ART 应用较远。
文献解读
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