Li Huirong, Cheng Linghui, Su Shiyue, Guo Peipei, Wei Zhaolian
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Anhui Province Key Laboratory of Reproductive Health and Genetics, Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, Hefei, Anhui Province, China.
Am J Reprod Immunol. 2023 Oct;90(4):e13765. doi: 10.1111/aji.13765.
Pyruvate dehydrogenase kinase 1 (PDK1) is an important enzyme for immune cell development. However, PDK1's role in human decidual natural killer (dNK) cells remains largely unknown.
PDK1 expression in dNK cells from patients with recurrent spontaneous abortions (RSA) and age-matched healthy controls was analyzed by qRT-PCR, western bolt and flow cytometry. Moreover, dNK cells were treated with PDK1 inhibitor or the PDK1 siRNA followed by functional assays.
The dNK cells from patients who underwent RSAs had higher mRNA expression and increased protein of PDK1, perforin (PRF1), Granzyme B (GZMB), IFN-γ (IFNG), and CD107a expression compared to dNK cells from age-matched healthy controls. Perforin, Granzyme B, IFN-γ and CD107a expression levels in dNK cells were down-regulated when dNK cells were treated with a PDK1 inhibitor. As measured by the Cr release assay, the killing activity of dNK cells was found to be decreased. We also demonstrated that PDK1 blockade could up-regulate the migration and adhesion of dNK cells. Furthermore, PDK1 inhibition reduced the glycolysis of dNK cells.
This study suggested that PDK1 plays an important role in regulating dNK cell functions and human RSA.
丙酮酸脱氢酶激酶1（PDK1）是免疫细胞发育的一种重要酶。然而，PDK1在人蜕膜自然杀伤（dNK）细胞中的作用仍 largely未知。
通过qRT-PCR、western bolt和流式细胞术分析复发性自然流产（RSA）患者和年龄匹配的健康对照者dNK细胞中PDK1的表达。此外，用PDK1抑制剂或PDK1 siRNA处理dNK细胞，然后进行功能测定。
与年龄匹配的健康对照者的dNK细胞相比，接受RSA的患者的dNK细胞具有更高的mRNA表达以及PDK1、穿孔素（PRF1）、颗粒酶B（GZMB）、干扰素-γ（IFNG）的蛋白表达增加和CD107a表达。当用PDK1抑制剂处理dNK细胞时，dNK细胞中穿孔素、颗粒酶B、干扰素-γ和CD107a的表达水平下调。通过铬释放试验测量，发现dNK细胞的杀伤活性降低。我们还证明，PDK1阻断可上调dNK细胞的迁移和黏附。此外，PDK1抑制降低了dNK细胞的糖酵解。
本研究表明，PDK1在调节dNK细胞功能和人类RSA中起重要作用。
