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

诱导性多能干细胞来源的髓系抑制细胞调节 CD8+ T 细胞反应

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作者:Daniel Joyce, Masayuki Fujino, Miwa Morita, Ryoko Araki, John Fung, Shiguang Qian, Lina Lu, Xiao-Kang Li

Abstract

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.

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