|
| Status |
Public on May 02, 2023 |
| Title |
Tolerogenic Dendritic Cells Engineered with IL-10 and Antigen Control Pathogenic T Cell Responses and Promote Type 1 T Regulatory Cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Dendritic cells (DC) play a critical role in the maintenance of tissue homeostasis and in promoting tolerance, thus acting as regulatory cells. Tolerogenic DC (tolDC) represent the cells of choice to fulfill the goal of restoring antigen (Ag)-specific tolerance since they can dampen Ag-specific T cell responses, induce pathogenic T cell exhaustion, and Ag-specific regulatory T cells. Here we efficiently generate tolDC by genetic engineering of monocytes with bidirectional lentiviral vectors co-encoding for immunodominant Ag-derived peptides (Ovalbumin or Matrix Protein 1, Insulin and Gliadin) in combination with IL-10 (DCIL-10/Ag). DCIL-10/Ag secrete high amounts of IL_x0002_10 in the absence of pro-inflammatory cytokines and efficiently modulate Ag-specific CD4+ and CD8+ T cell activation and proliferation in vitro in healthy subjects and Celiac Disease patients. DCIL-10/Ag promote Ag-specific CD49b+LAG-3 + T cells, which display the type 1 T regulatory (Tr1) cell gene signature in vitro. In vivo administration of DCIL-10/Ag promote Ag-specific Tr1 cells and prevent type 1 diabetes development in two murine models of disease. In conclusion, we generate an innovative approach based on the use of autologous engineered DC, which effectively modulate pathogenic CD4+ and CD8+ T cell responses in vitro and in vivo by promoting Ag_x0002_specific Tr1 cells suitable for cell-based therapy for restoring tolerance in T cell mediated diseases
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| |
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| Overall design |
RNA-Seq of 6 samples from 3 independent donors; from each donor 1 Control and 1 test sample were generated
|
| Web link |
https://pubmed.ncbi.nlm.nih.gov/37224733/
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| |
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| Contributor(s) |
Passerini L, Andolfi G, Passeri L, Gregori S, Giacomini G |
| Citation(s) |
37224733 |
| |
| Submission date |
Mar 25, 2022 |
| Last update date |
Jan 16, 2024 |
| Contact name |
Silvia Gregori |
| E-mail(s) |
gregori.silvia@hsr.it
|
| Organization name |
SR-TIGET
|
| Lab |
Mechanisms of Peripheral Tolerance
|
| Street address |
Via Olgettina 60
|
| City |
Milano |
| State/province |
Italy |
| ZIP/Postal code |
20132 |
| Country |
Italy |
| |
|
| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
| Samples (6)
|
| GSM5972561 |
CD3+CD4+CD49b+LAG3+ Ag-specific Tr1 cells (T(DCIL-10/Ins) EXP85 |
| GSM5972562 |
CD3+CD4+CD49b+LAG3+ Ag-specific Tr1 cells (T(DCIL-10/Ins) EXP86 |
| GSM5972563 |
CD3+CD4+CD49b+LAG3+ Ag-specific Tr1 cells (T(DCIL-10/Ins) EXP87 |
| GSM5972564 |
CD3+CD4+Ag-specific non-Tr1 cells (T(DCIns)) EXP85 |
| GSM5972565 |
CD3+CD4+Ag-specific non-Tr1 cells (T(DCIns)) EXP86 |
| GSM5972566 |
CD3+CD4+Ag-specific non-Tr1 cells (T(DCIns)) EXP87 |
|
| Relations |
| BioProject |
PRJNA819976 |
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