論文 - 詳細
| RRC ID | 54879 |
|---|---|
| 著者 | Haque M, Lei F, Xiong X, Das JK, Ren X, Fang D, Salek-Ardakani S, Yang JM, Song J. |
| タイトル | Stem cell-derived tissue-associated regulatory T cells suppress the activity of pathogenic cells in autoimmune diabetes. |
| ジャーナル | JCI Insight |
| Abstract |
The autoantigen-specific Tregs from pluripotent stem cells (PSCs), i.e., PSC-Tregs, have the ability to suppress autoimmunity. PSC-Tregs can be programmed to be tissue associated and to infiltrate into local inflamed tissues to suppress autoimmune responses after adoptive transfer. Nevertheless, the mechanisms by which the autoantigen-specific PSC-Tregs suppress the autoimmune response remain to be fully elucidated. In this study, we generated functional autoantigen-specific Tregs from the induced PSC (iPSCs), i.e., iPSC-Tregs, and investigated the underlying mechanisms of autoimmunity suppression by these Tregs in a type 1 diabetes (T1D) murine model. A double-Tg mouse model of T1D was established in F1 mice, in which the first generation of RIP-mOVA Tg mice that were crossed with OT-I T cell receptor (TCR) Tg mice was challenged with vaccinia viruses expressing OVA (VACV-OVA). We show that adoptive transfer of OVA-specific iPSC-Tregs greatly suppressed autoimmunity in the animal model and prevented the insulin-secreting pancreatic β cells from destruction. Further, we demonstrate that the adoptive transfer significantly reduced the expression of ICAM-1 in the diabetic pancreas and inhibited the migration of pathogenic CD8+ T cells and the production of the proinflammatory IFN-γ in the pancreas. These results indicate that the stem cell-derived tissue-associated Tregs can robustly accumulate in the diabetic pancreas, and, through downregulating the expression of ICAM-1 in the local inflamed tissues and inhibiting the production of proinflammatory cytokine IFN-γ, suppress the migration and activity of the pathogenic immune cells that cause T1D. |
| 巻・号 | 4(7) |
| 公開日 | 2019-4-4 |
| DOI | 10.1172/jci.insight.126471 |
| PII | 126471 |
| PMID | 30777937 |
| PMC | PMC6483657 |
| MeSH | Adoptive Transfer / methods* Animals Autoimmunity* Cell Differentiation Cell Line Cell Movement / immunology Diabetes Mellitus, Type 1 / genetics Diabetes Mellitus, Type 1 / immunology Diabetes Mellitus, Type 1 / pathology Diabetes Mellitus, Type 1 / therapy* Disease Models, Animal Down-Regulation Humans Induced Pluripotent Stem Cells Intercellular Adhesion Molecule-1 / immunology Intercellular Adhesion Molecule-1 / metabolism Interferon-gamma / immunology Interferon-gamma / metabolism Mice Mice, Transgenic Pancreas / immunology Pancreas / pathology T-Lymphocytes, Regulatory / immunology T-Lymphocytes, Regulatory / transplantation* |
| IF | 6.205 |
| 引用数 | 3 |
| 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 | X(Twitter) |
| 各媒体での言及数の合計 | 7 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | iPS-MEF-Ng-20D-17(APS0001) |