Induced pluripotent stem cells-derived myeloid-derived suppressor cells regulate the CD8+ T cell response

• Published in: Stem cell research 2018-05, Vol.29, p.32-41
• Main Authors: Joyce, Daniel, Fujino, Masayuki, Morita, Miwa, Araki, Ryoko, Fung, John, Qian, Shiguang, Lu, Lina, Li, Xiao-Kang
• Format: Article
• Language: English
• Subjects: Induced pluripotent stem cells; Myeloid-derived suppressor cells; T cell response
• ISSN: 1873-5061; 1876-7753
• DOI: 10.1016/j.scr.2018.03.009

Myeloid-derived suppressor cells (MDSCs) are markedly increased in cancer patients and tumor-bearing mice and promote tumor growth and survival by inhibiting host innate and adaptive immunity. In this study, we generated and characterized MDSCs from murine-induced pluripotent stem cells (iPSCs). The iPSCs were co-cultured with OP9 cells, stimulated with GM-CSF, and became morphologically heterologous under co-culturing with hepatic stellate cells. Allogeneic and OVA-specific antigen stimulation demonstrated that iPS-MDSCs have a T-cell regulatory function. Furthermore, a popliteal lymph node assay and autoimmune hepatitis model showed that iPS-MDSCs also regulate immune responsiveness in vivo and have a therapeutic effect against hepatitis. Taken together, our results demonstrated a method of generating functional MDSCs from iPSCs and highlighted the potential of iPS-MDSCs as a key cell therapy resource for transplantation and autoimmune diseases. •MDSCs were successfully generated from iPSCs.•iPS-MDSCs were able to inhibit T-cell responses in vitro and in vivo.•iPS-MDSCs diminished CD8+ T cell infiltration and ALT leakage in an autoimmune hepatitis murine model.