Pyruvate dehydrogenase kinase 1 regulates the function of human decidual natural killer cells

Abstract

AbstractProblemPyruvate 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.Methods of studyPDK1 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.ResultsThe 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 51Cr 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.ConclusionThis study suggested that PDK1 plays an important role in regulating dNK cell functions and human RSA.