NANOG has a role in mesenchymal stem cells' immunomodulatory effect

Abstract

It is well known that terminally differentiated cells derived from mesenchymal stem cells (MSCs) will lose the immunomodulation capacity. NANOG is known to be a core transcription factor in the maintenance of stem cell specific features or stemness. To evaluate whether NANOG was involved in the immunomodulation effects of MSCs, MSCs' immunomodulation capacity on lymphocyte activation and proliferation before or after endogenous NANOG interference was investigated. We found that MSCs' inhibitory effects on lymphocyte activation and proliferation was significantly weakened after NANOG knockdown. In addition, NANOG RNAi and chromatin immunoprecipitation experiments showed that NANOG suppressed the expression and secretion of DKK-1, transforming growth factor-beta1 (TGF-β1), TGF-β2, and TGF-β3, which are all important factors mediating MSCs' immunomodulation capacity. Based on these data, we propose that NANOG plays an important role in maintaining the immunomodulation functions of MSCs by regulating the expression and secretion of TGF-β1, TGF-β2, TGF-β3, and DKK-1.