Stem cell-derived tissue-associated regulatory T cells ameliorate the development of autoimmunity

Mohammad Haque, Jianyong Song, Kristin Fino, Praneet Sandhu, Xinmeng Song, Fengyang Lei, Songguo Zheng, Bing Ni, Deyu Fang, Jianxun Song

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number20588
JournalScientific reports
Volume6
DOIs
StatePublished - Feb 5 2016

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Pluripotent Stem Cells
Regulatory T-Lymphocytes
Autoimmunity
Stem Cells
Viral Tumor Antigens
Antigens
Adoptive Transfer
Arthritis
Induced Pluripotent Stem Cells
Osteoclasts
Immunosuppressive Agents
T-Cell Antigen Receptor
Immunosuppression
Prostaglandins
Cartilage
Joints
Inflammation
Therapeutics
Genes

All Science Journal Classification (ASJC) codes

  • General

Cite this

Haque, M., Song, J., Fino, K., Sandhu, P., Song, X., Lei, F., ... Song, J. (2016). Stem cell-derived tissue-associated regulatory T cells ameliorate the development of autoimmunity. Scientific reports, 6, [20588]. https://doi.org/10.1038/srep20588
Haque, Mohammad ; Song, Jianyong ; Fino, Kristin ; Sandhu, Praneet ; Song, Xinmeng ; Lei, Fengyang ; Zheng, Songguo ; Ni, Bing ; Fang, Deyu ; Song, Jianxun. / Stem cell-derived tissue-associated regulatory T cells ameliorate the development of autoimmunity. In: Scientific reports. 2016 ; Vol. 6.
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abstract = "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.",
author = "Mohammad Haque and Jianyong Song and Kristin Fino and Praneet Sandhu and Xinmeng Song and Fengyang Lei and Songguo Zheng and Bing Ni and Deyu Fang and Jianxun Song",
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Haque, M, Song, J, Fino, K, Sandhu, P, Song, X, Lei, F, Zheng, S, Ni, B, Fang, D & Song, J 2016, 'Stem cell-derived tissue-associated regulatory T cells ameliorate the development of autoimmunity', Scientific reports, vol. 6, 20588. https://doi.org/10.1038/srep20588

Stem cell-derived tissue-associated regulatory T cells ameliorate the development of autoimmunity. / Haque, Mohammad; Song, Jianyong; Fino, Kristin; Sandhu, Praneet; Song, Xinmeng; Lei, Fengyang; Zheng, Songguo; Ni, Bing; Fang, Deyu; Song, Jianxun.

In: Scientific reports, Vol. 6, 20588, 05.02.2016.

Research output: Contribution to journalArticle

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AU - Haque, Mohammad

AU - Song, Jianyong

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AU - Song, Xinmeng

AU - Lei, Fengyang

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AU - Ni, Bing

AU - Fang, Deyu

AU - Song, Jianxun

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