PMID- 18981145
OWN - NLM
STAT- MEDLINE
DCOM- 20081212
LR  - 20190516
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 181
IP  - 10
DP  - 2008 Nov 15
TI  - Dendritic cells genetically engineered to express IL-10 induce long-lasting 
      antigen-specific tolerance in experimental asthma.
PG  - 7230-42
AB  - 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.
FAU - Henry, Emmanuelle
AU  - Henry E
AD  - Laboratoire de Physiologie Animale, Institut de Biologie et de Medecine 
      Moleculaires, Universite Libre de Bruxelles, Gosselies, Belgium.
FAU - Desmet, Christophe J
AU  - Desmet CJ
FAU - Garze, Virginie
AU  - Garze V
FAU - Fievez, Laurence
AU  - Fievez L
FAU - Bedoret, Denis
AU  - Bedoret D
FAU - Heirman, Carlo
AU  - Heirman C
FAU - Faisca, Pedro
AU  - Faisca P
FAU - Jaspar, Fabrice J
AU  - Jaspar FJ
FAU - Gosset, Philippe
AU  - Gosset P
FAU - Jacquet, Alain P A
AU  - Jacquet AP
FAU - Desmecht, Daniel
AU  - Desmecht D
FAU - Thielemans, Kris
AU  - Thielemans K
FAU - Lekeux, Pierre
AU  - Lekeux P
FAU - Moser, Muriel
AU  - Moser M
FAU - Bureau, Fabrice
AU  - Bureau F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Antigens)
RN  - 130068-27-8 (Interleukin-10)
RN  - 9006-59-1 (Ovalbumin)
SB  - IM
MH  - Adoptive Transfer
MH  - Animals
MH  - Antigens/immunology
MH  - Apoptosis/immunology
MH  - Asthma/immunology/*metabolism/therapy
MH  - Cells, Cultured
MH  - Dendritic Cells/immunology/*metabolism
MH  - Disease Models, Animal
MH  - Female
MH  - Flow Cytometry
MH  - Genetic Engineering/*methods
MH  - *Immune Tolerance
MH  - Immunotherapy/methods
MH  - Interleukin-10/genetics/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Ovalbumin/immunology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - T-Lymphocytes, Regulatory/immunology
MH  - Transduction, Genetic
EDAT- 2008/11/05 09:00
MHDA- 2008/12/17 09:00
CRDT- 2008/11/05 09:00
PHST- 2008/11/05 09:00 [pubmed]
PHST- 2008/12/17 09:00 [medline]
PHST- 2008/11/05 09:00 [entrez]
AID - 181/10/7230 [pii]
AID - 10.4049/jimmunol.181.10.7230 [doi]
PST - ppublish
SO  - J Immunol. 2008 Nov 15;181(10):7230-42. doi: 10.4049/jimmunol.181.10.7230.