TY - JOUR
T1 - Stem cell-derived tissue-associated regulatory T cells ameliorate the development of autoimmunity
AU - Haque, Mohammad
AU - Song, Jianyong
AU - Fino, Kristin
AU - Sandhu, Praneet
AU - Song, Xinmeng
AU - Lei, Fengyang
AU - Zheng, Songguo
AU - Ni, Bing
AU - Fang, Deyu
AU - Song, Jianxun
N1 - Funding Information:
We thank the cores of Molecular and Histopathology and Flow Cytometry at The Pennsylvania State University College of Medicine for providing the histologic staining and cell sorting. This project was funded, in part, under grants with the National Institute of Health Grant R21AI109239 and K18CA151798, Leona M. and Harry B. Helmsley Charitable Trust 2014PG-T1D049, and the Pennsylvania Department of Health using Tobacco Settlement Fund SAP # 4100057673 to J.S.
PY - 2016/2/5
Y1 - 2016/2/5
N2 - Pluripotent stem cells (PSCs) have the potential to produce almost all of the cells in the body, including regulatory T cells (T regs). However, the exact conditions required for the development of antigen (Ag)-specific T regs from PSCs (i.e., PSC-T regs) are not well delineated. Ag-specific PSC-T regs can be tissue/organ-associated and migrate to local inflamed tissues/organs to suppress the autoimmune response after adoptive transfer, thereby avoiding potential overall immunosuppression from non-specific T regs. In this study, we developed a new approach to generate functional Ag-specific T regs from induced PSCs (iPSCs), i.e., iPSC-T regs, which had the ability to generate an Ag-specific immunosuppressive response in a murine model of arthritis. We retrovirally transduced murine iPSCs with a construct containing genes of Ag-specific T cell receptor (TCR) and the transcriptional factor FoxP3. We differentiated the iPSCs into Ag-specific iPSC-T regs using in vitro or in vivo Notch signaling, and demonstrated that adoptive transfer of such T regs dramatically suppressed autoimmunity in a well-established Ag-induced arthritis model, including the inflammation, joint destruction, cartilage prostaglandin depletion, osteoclast activity, and Th17 production. Our results indicate that PSCs can be used to develop Ag-specific T regs, which have a therapeutic potential for T reg-based therapies of autoimmune disorders.
AB - Pluripotent stem cells (PSCs) have the potential to produce almost all of the cells in the body, including regulatory T cells (T regs). However, the exact conditions required for the development of antigen (Ag)-specific T regs from PSCs (i.e., PSC-T regs) are not well delineated. Ag-specific PSC-T regs can be tissue/organ-associated and migrate to local inflamed tissues/organs to suppress the autoimmune response after adoptive transfer, thereby avoiding potential overall immunosuppression from non-specific T regs. In this study, we developed a new approach to generate functional Ag-specific T regs from induced PSCs (iPSCs), i.e., iPSC-T regs, which had the ability to generate an Ag-specific immunosuppressive response in a murine model of arthritis. We retrovirally transduced murine iPSCs with a construct containing genes of Ag-specific T cell receptor (TCR) and the transcriptional factor FoxP3. We differentiated the iPSCs into Ag-specific iPSC-T regs using in vitro or in vivo Notch signaling, and demonstrated that adoptive transfer of such T regs dramatically suppressed autoimmunity in a well-established Ag-induced arthritis model, including the inflammation, joint destruction, cartilage prostaglandin depletion, osteoclast activity, and Th17 production. Our results indicate that PSCs can be used to develop Ag-specific T regs, which have a therapeutic potential for T reg-based therapies of autoimmune disorders.
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U2 - 10.1038/srep20588
DO - 10.1038/srep20588
M3 - Article
C2 - 26846186
AN - SCOPUS:84957577355
SN - 2045-2322
VL - 6
JO - Scientific Reports
JF - Scientific Reports
M1 - 20588
ER -