Dendritic cells genetically engineered to express IL-10 induce long-lasting antigen-specific tolerance in experimental asthma.
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.
Henry
Emmanuelle
E
Laboratoire de Physiologie Animale, Institut de Biologie et de Médecine Moléculaires, Université Libre de Bruxelles, Gosselies, Belgium.
Desmet
Christophe J
CJ
Garzé
Virginie
V
Fiévez
Laurence
L
Bedoret
Denis
D
Heirman
Carlo
C
Faisca
Pedro
P
Jaspar
Fabrice J
FJ
Gosset
Philippe
P
Jacquet
Alain P A
AP
Desmecht
Daniel
D
Thielemans
Kris
K
Lekeux
Pierre
P
Moser
Muriel
M
Bureau
Fabrice
F
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
D000941:Antigens; D016753:Interleukin-10; D010047:Ovalbumin