Dendritic cells genetically engineered to express IL-10 induce long-lasting antigen-specific tolerance in experimental asthma
| Autor: | Pierre Lekeux, Fabrice Jaspar, Muriel Moser, Emmanuelle Henry, Daniel Desmecht, Kris Thielemans, Pedro Faísca, Christophe Desmet, Laurence Fievez, Alain Jacquet, Philippe Gosset, Carlo Heirman, Denis Bedoret, Fabrice Bureau, Virginie Garzé |
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| Přispěvatelé: | Physiology |
| Předmět: |
Adoptive cell transfer
Ovalbumin medicine.medical_treatment Immunology Apoptosis Biology T-Lymphocytes Regulatory Immune tolerance Mice Immune system Transduction Genetic medicine Immune Tolerance Immunology and Allergy Animals IL-2 receptor dendritic cells Antigens Cells Cultured Mice Knockout Reverse Transcriptase Polymerase Chain Reaction FOXP3 respiratory system asthma Flow Cytometry Adoptive Transfer Interleukin-10 Interleukin 10 Disease Models Animal Cytokine Mediastinal lymph node IL-10 Female Immunotherapy Genetic Engineering |
| Zdroj: | ResearcherID |
| Popis: | Dendritic cells (DCs) are professional APCs that have a unique capacity to initiate primary immune responses, including tolerogenic responses. We have genetically engineered bone marrow-derived DCs to express the immunosuppressive cytokine IL-10 and tested the ability of these cells to control experimental asthma. A single intratracheal injection of OVA-pulsed IL-10-transduced DCs (OVA-IL-10-DCs) to naive mice before OVA sensitization and challenge prevented all of the cardinal features of airway allergy, namely, eosinophilic airway inflammation, airway hyperreactivity, and production of mucus, Ag-specific Igs, and IL-4. OVA-IL-10-DCs also reversed established experimental asthma and had long-lasting and Ag-specific effects. We furthermore showed, by using IL-10-deficient mice, that host IL-10 is required for mediating the immunomodulatory effects of OVA-IL-10-DCs and demonstrated a significant increase in the percentage of OVA-specific CD4+CD25+Foxp3+IL-10+ regulatory T cells in the mediastinal lymph nodes of OVA-IL-10-DC-injected mice. Finally, adoptive transfer of CD4+ mediastinal lymph node T cells from mice injected with OVA-IL-10-DCs protected OVA-sensitized recipients from airway eosinophilia upon OVA provocation. Our study describes a promising strategy to induce long-lasting Ag-specific tolerance in airway allergy. |
| Databáze: | OpenAIRE |
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