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

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

Stem Cell Research (May 2018)

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

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

Affiliations

Daniel Joyce: Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Department of General Surgery, Cleveland Clinic, Cleveland, OH, USA
Masayuki Fujino: Laboratory of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo, Japan; AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan
Miwa Morita: Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Department of General Surgery, Cleveland Clinic, Cleveland, OH, USA
Ryoko Araki: Department of Basic Medical Sciences for Radiation Damages, National Institute of Radiological Sciences, Chiba, Japan
John Fung: Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
Shiguang Qian: Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Department of General Surgery, Cleveland Clinic, Cleveland, OH, USA
Lina Lu: Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Department of General Surgery, Cleveland Clinic, Cleveland, OH, USA; Correspondence to: L. Lu, Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, 9550 Euclid Ave. NB30, OH 44195, USA.
Xiao-Kang Li: Laboratory of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo, Japan; Correspondence to: X. K. Li Division of Transplantation Immunology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, Japan.

Journal volume & issue: Vol. 29
pp. 32 – 41

Abstract

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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. Keywords: Myeloid-derived suppressor cells, Induced pluripotent stem cells, T cell response

Published in Stem Cell Research

ISSN: 1873-5061 (Print); 1876-7753 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: https://www.journals.elsevier.com/stem-cell-research

About the journal