論文 - 詳細
| RRC ID | 64977 |
|---|---|
| 著者 | Haque M, Song J, Fino K, Sandhu P, Song X, Lei F, Zheng S, Ni B, Fang D, Song J. |
| タイトル | Stem cell-derived tissue-associated regulatory T cells ameliorate the development of autoimmunity. |
| ジャーナル | Sci Rep |
| Abstract |
Pluripotent stem cells (PSCs) have the potential to produce almost all of the cells in the body, including regulatory T cells (Tregs). However, the exact conditions required for the development of antigen (Ag)-specific Tregs from PSCs (i.e., PSC-Tregs) are not well delineated. Ag-specific PSC-Tregs 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 Tregs. In this study, we developed a new approach to generate functional Ag-specific Tregs from induced PSCs (iPSCs), i.e., iPSC-Tregs, 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-Tregs using in vitro or in vivo Notch signaling, and demonstrated that adoptive transfer of such Tregs 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 Tregs, which have a therapeutic potential for Treg-based therapies of autoimmune disorders. |
| 巻・号 | 6 |
| ページ | 20588 |
| 公開日 | 2016-2-5 |
| DOI | 10.1038/srep20588 |
| PII | srep20588 |
| PMID | 26846186 |
| PMC | PMC4742827 |
| MeSH | Adoptive Transfer / methods* Animals Arthritis, Experimental / immunology Arthritis, Experimental / therapy* Autoimmunity* Cell Line Cells, Cultured Coculture Techniques Disease Models, Animal Forkhead Transcription Factors / genetics Forkhead Transcription Factors / metabolism Induced Pluripotent Stem Cells / cytology* Mice Receptors, Antigen, T-Cell / genetics Receptors, Antigen, T-Cell / metabolism T-Lymphocytes, Regulatory / cytology* T-Lymphocytes, Regulatory / immunology Transduction, Genetic |
| IF | 3.998 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 6 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 3.0 |
| リソース情報 | |
| ヒト・動物細胞 | iPS-MEF-Ng-20D-17(APS0001) |