| 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
|
| リソース情報 |
| ヒト・動物細胞 |
iPS-MEF-Ng-20D-17(APS0001) |
