| RRC ID |
54879
|
| Author |
Haque M, Lei F, Xiong X, Das JK, Ren X, Fang D, Salek-Ardakani S, Yang JM, Song J.
|
| Title |
Stem cell-derived tissue-associated regulatory T cells suppress the activity of pathogenic cells in autoimmune diabetes.
|
| Journal |
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.
|
| Volume |
4(7)
|
| Published |
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
|
| Times Cited |
3
|
| Resource |
| Human and Animal Cells |
iPS-MEF-Ng-20D-17(APS0001) |
