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See detailDendritic cells genetically engineered to express IL-10 induce long-lasting antigen-specific tolerance in experimental asthma.
Henry, E.; Desmet, Christophe ULiege; Garze, V. et al

in Journal of Immunology (2008), 181(10), 7230-7242

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 ... [more ▼]

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. [less ▲]

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See detailSTAT5 is an Ambivalent Regulator of Neutrophil Homeostasis
Fievez, Laurence ULiege; Desmet, Christophe ULiege; Henry, E. et al

Poster (2007)

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See detailDendritic cells genetically engineered to express IL-10 induce long-lasting antigen-specific tolerance in experimental asthma
Henry, E.; Desmet, C. J.; Garzé, V. et al

Poster (2007)

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See detailSelective inhibition of AP-1 activity in airway immune cells ameliorates experimental asthma
Desmet, Christophe ULiege; Gosset, P.; Garzé, V. et al

in Proceedings: The American Thoracic Society (2005)

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See detailTreatment of experimental asthma by decoy-mediated local inhibition of activator protein-1
Desmet, Christophe ULiege; Gosset, P.; Henry, E. et al

in American Journal of Respiratory and Critical Care Medicine (2005), 172(6), 671-678

Rationale: Asthma is associated with increased expression of a typical array of genes involved in immune and inflammatory responses, including those encoding the prototypic Th2 cytokines interleukin (IL ... [more ▼]

Rationale: Asthma is associated with increased expression of a typical array of genes involved in immune and inflammatory responses, including those encoding the prototypic Th2 cytokines interleukin (IL) 4, IL-5, and IL-13. Most of these genes contain binding sites for activator protein-1 (AP-1) within their promoter and are therefore believed to depend on AP-1 for their expression, suggesting that this transcription factor could be of particular importance in asthma pathophysiology. Objective: To clarify the role of AP-1 in the effector phase of pulmonary allergy. Methods: Ovalbumin (OVA)-sensitized mice were intratracheally given decoy oligodeoxyribonucleotides (ODNs) specifically directed to AP-1 or scrambled control ODNs before challenge with aerosolized OVA. Twenty-four hours after the last OVA challenge, airway hyperresponsiveness was measured and allergic airway inflammation was evaluated quantitatively. AP-1 decoys were localized using flow cytometry and immunohistochemistry. AP-1 activity in the lung was assessed using electrophoretic mobility shift assay. Measurements and Main Results: Intratracheally delivered AP-1 decoys efficiently targeted airway immune cells, thus precluding AP-1 activation on OVA challenge. Decoy-mediated local inhibition of AP-1 resulted in significant attenuation of all the pathophysiologic features of experimental asthma-namely, eosinophilic airway inflammation, airway hyperresponsiveness, mucous cell hyperplasia, production of allergen-specific immunoglobulins, and synthesis of IL-4, IL-5, and IL-13. Scrambled control ODNs had no detectable effects. Conclusions: Our results reveal a key role for AP-1 in the effector phase of pulmonary allergy and indicate that specific AP-1 inhibition in the airways may have therapeutic value in the control of established asthma. [less ▲]

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See detailSelective decoy-mediated inhibition of activator protein-1 activity in the airways pevents experimental asthmatic inflammation
Desmet, Christophe ULiege; Gosset, P.; Pajak, B. et al

in European Respiratory Journal (2005), 26

Detailed reference viewed: 14 (5 ULiège)