JAK/STAT signaling pathway involved in NK cell differentiation of CD117+ expressing progenitor cells

JAK/STAT signaling pathway involved in NK cell differentiation of CD117+ expressing progenitor cells
Ezzatollah Fathi,¹ Behnaz Valipour,² Raheleh Farahzadi,^3,*
1. Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran
2. Department of Histopathology and Anatomy, Faculty of Medicine, Tabriz Branch, Islamic Azad University, Tabriz, Iran
3. Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Introduction: Natural killer (NK) cells are the first body defensive line in destroying cancerous cells and virus infected cells. Reducing the activity of these cells can be associated with the incidence, deployment and spread of many cancers such as leukemia and autoimmune diseases. Also, hematopoietic stem cells transplantation is used to treat a wide range of patients such as hereditary anemia as well as blood malignant disorders. Previous in vitro studies have shown that using specific fundamental factors, bone marrow lineage hematopoietic stem cells can be differentiating into the NK cells. Notably, the use of NK cells for cell therapy relies on the availability of a great number of NK cells with optimal cytotoxic activity. Obtaining a large number of NK cells as well as the understanding and investigating the cellular and molecular mechanisms involved in stem cell differentiating is an important.
Methods: For this purpose, mononuclear cells (MNCs) were isolated from rat bone marrow by Ficoll-Hypaque gradient centrifugation and CD117+ cells were enriched by MACS method. In the following, CD117+ cells were treated in the presence of NK differential factors such as SCF (kit ligand), FLT3 and IL-15 for 21 days. At the end of culture period, the gene and protein expression of JAK and STAT were investigated by real-time PCR and western blotting, respectively.
Results: It was shown that NK cell differentiated cells were significantly expressed the gene and proteins JAK and STAT compared to CD117+ progenitor expressing cells
Conclusion: It was concluded that the CD117+ cells as hematopoietic progenitor cells could differentiate to NK cells. The current results also showed that the NK cell differentiation of CD117+ progenitor expressing cells could be through activation of JAK/STAT signaling pathway.
Keywords: NK cells, NK cell differentiation, CD177+ progenitor expressing cells, JAK/STAT signaling pathway