title: Dendritic cells genetically engineered to express IL-10 induce long-lasting antigen-specific tolerance in experimental asthma.
abstract: 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.
authors.affiliation: Laboratoire de Physiologie Animale, Institut de Biologie et de Médecine Moléculaires, Université Libre de Bruxelles, Gosselies, Belgium.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Henry
authors.forename: Christophe J
authors.initials: CJ
authors.lastname: Desmet
authors.forename: Virginie
authors.initials: V
authors.lastname: Garzé
authors.forename: Laurence
authors.initials: L
authors.lastname: Fiévez
authors.forename: Denis
authors.initials: D
authors.lastname: Bedoret
authors.forename: Carlo
authors.initials: C
authors.lastname: Heirman
authors.forename: Pedro
authors.initials: P
authors.lastname: Faisca
authors.forename: Fabrice J
authors.initials: FJ
authors.lastname: Jaspar
authors.forename: Philippe
authors.initials: P
authors.lastname: Gosset
authors.forename: Alain P A
authors.initials: AP
authors.lastname: Jacquet
authors.forename: Daniel
authors.initials: D
authors.lastname: Desmecht
authors.forename: Kris
authors.initials: K
authors.lastname: Thielemans
authors.forename: Pierre
authors.initials: P
authors.lastname: Lekeux
authors.forename: Muriel
authors.initials: M
authors.lastname: Moser
authors.forename: Fabrice
authors.initials: F
authors.lastname: Bureau
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000941:Antigens / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D001249:Asthma / Q000276:immunology / Q000378:metabolism* / Q000628:therapy; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D005818:Genetic Engineering / Q000379:methods*; D007108:Immune Tolerance; D007167:Immunotherapy / Q000379:methods; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014161:Transduction, Genetic
chemical_list: D000941:Antigens; D016753:Interleukin-10; D010047:Ovalbumin