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See detailInterferon Response Factor 3 is essential for house dust mite-induced airway allergy
Marichal, Thomas ULg; Bedoret, Denis; Mesnil, Claire et al

Conference (2011, May)

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See detailIRF3 is essential for house dust mite-induced airway allergy in mice
Marichal, Thomas ULg; Bedoret, Denis; Mesnil, Claire ULg et al

in Proceedings GIGA-Day 2011 (2011, May)

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See detailSirtuin 1 Promotes Th2 Responses and Airway Allergy by Repressing Peroxisome Proliferator-Activated Receptor-γ Activity in Dendritic Cells
Legutko, Agnieszka; Marichal, Thomas ULg; Fievez, Laurence ULg et al

in Journal of Immunology (2011), 187(9), 4517-4529

Sirtuins are a unique class of NAD+-dependent deacetylases that regulate diverse biological functions such as aging, metabolism, and stress resistance. Recently, it has been shown that sirtuins may have ... [more ▼]

Sirtuins are a unique class of NAD+-dependent deacetylases that regulate diverse biological functions such as aging, metabolism, and stress resistance. Recently, it has been shown that sirtuins may have anti-inflammatory activities by inhibiting proinflammatory transcription factors such as NF-κB. In contrast, we report in this study that pharmacological inhibition of sirtuins dampens adaptive Th2 responses and subsequent allergic inflammation by interfering with lung dendritic cell (DC) function in a mouse model of airway allergy. Using genetic engineering, we demonstrate that sirtuin 1 represses the activity of the nuclear receptor peroxisome proliferator-activated receptor-γ in DCs, thereby favoring their maturation toward a pro-Th2 phenotype. This study reveals a previously unappreciated function of sirtuin 1 in the regulation of DC function and Th2 responses, thus shedding new light on our current knowledge on the regulation of inflammatory processes by sirtuins. [less ▲]

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See detailADAM-8, a metalloproteinase, drives acute allergen-induced airway inflammation
Paulissen, Geneviève ULg; Rocks, Natacha ULg; Guéders, Maud ULg et al

in European Journal of Immunology (2011), 41(2), 380-91

Asthma is a complex disease linked to various pathophysiological events including the activity of proteinases. The multifunctional A Disintegrin And Metalloproteinases (ADAMs) displaying the ability to ... [more ▼]

Asthma is a complex disease linked to various pathophysiological events including the activity of proteinases. The multifunctional A Disintegrin And Metalloproteinases (ADAMs) displaying the ability to cleave membrane-bound mediators or cytokines appear to be key mediators in various inflammatory processes. In the present study, we have investigated ADAM-8 expression and production in a mouse model of allergen-induced airway inflammation. In allergen-exposed animals, increased expression of ADAM-8 was found in the lung parenchyma and in dendritic cells purified from the lungs. The potential role of ADAM-8 in the development of allergen-induced airway inflammation was further investigated by the use of an anti-ADAM-8 antibody and ADAM-8 knock-out animals. We observed a decrease in allergen-induced acute inflammation both in BALF and the peribronchial area in anti-ADAM-8 antibody-treated mice and in ADAM-8 deficient mice (ADAM-8-/-) after allergen exposure. ADAM-8 depletion led to a significant decrease of the CD11c+ lung dendritic cells. We also report lower levels of CCL11 and CCL22 production in antibody-treated mice and ADAM-8-/- mice that might be explained by decreased eosinophilic inflammation and lower numbers of dendritic cells, respectively. In conclusion, ADAM-8 appears to favour allergen-induced acute airway inflammation by promoting dendritic cell recruitment and CCL11 and CCL22 production. [less ▲]

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See detailRelease and innate immune detection of host cell DNA mediate the adjuvant activity of aluminum salts
Marichal, Thomas ULg; Ohata, K; Bedoret, D et al

Poster (2011)

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See detailRelease and innate immune detection of host cell DNA mediate the adjuvant activity of aluminum salts
Marichal, Thomas ULg; Ohata, K; Bedoret, Denis et al

Conference (2011)

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See detailSelf-DNA release mediates the adjuvant effects of aluminum salts
Marichal, Thomas ULg; Ohata, K; Bedoret, Denis et al

Poster (2011)

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See detailInvestigation of the innate immunity in the lower respiratory tract in exercising horses
Frellstedt, Linda ULg; Gosset, Philippe; Desmet, Christophe ULg et al

in Proceedings of the 1st Scientific Meeting of the Faculty of Veterinary Medicine (2011)

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See detailInterferon Response Factor 3 is required for airway allergy to house dust mite in mice
Marichal, Thomas ULg; Bedoret Denis; Mesnil, Claire ULg et al

in Short Book of the Annual Congress of the Euopean Respiratory Society (ERS), Barcelone (2010, September)

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See detailRelease and innate detection of hot cell DNA mediates the adjuvant effects of aluminium salts on adaptive responses.
Marichal, Thomas ULg; Ohata, Keichii; Bedoret, Denis et al

Conference (2010, February)

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See detailInterferon Response Factor 3 is essential for house dust mite-induced airway allergy
Marichal, Thomas ULg; Bedoret, Denis; Mesnil, Claire ULg et al

in Journal of Allergy and Clinical Immunology (The) (2010), 126(4), 836-844

IRF3, mainly known as a central orchestrator of antiviral responses, is required for proallergic functions of dendritic cells in response to aeroallergens. Thus, this study demonstratively identifies a ... [more ▼]

IRF3, mainly known as a central orchestrator of antiviral responses, is required for proallergic functions of dendritic cells in response to aeroallergens. Thus, this study demonstratively identifies a new pathway potentially implicated in the etiology of airway allergy [less ▲]

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See detailViral induction of Zac1b through TLR3- and IRF3-dependent pathways
Warzée, Barbara ULg; Mesnil, Claire ULg; Hober, D. et al

in Molecular Immunology (2010), 48(1-3), 119-127

Zinc finger protein regulator of apoptosis and cell cycle arrest (Zac1) is a transcription factor able to induce apoptosis or cell cycle arrest through independent pathways. In spite of the important ... [more ▼]

Zinc finger protein regulator of apoptosis and cell cycle arrest (Zac1) is a transcription factor able to induce apoptosis or cell cycle arrest through independent pathways. In spite of the important potential functions attributed to Zac1, little is known of its physiological regulation and biological function. We discovered that variant Zac1b was expressed in murine embryonic fibroblasts (MEFs) treated with polyriboinosinic polyribocytidylic acid [poly(I:C)], a synthetic double-stranded RNA. This regulation occurred mainly through Toll-Like Receptor 3 (TLR3)- and Interferon Regulatory Factor 3 (IRF3)-dependent pathways. As TLR3 and IRF3 are central activators of antiviral immunity, we hypothesized that Zac1 may be implicated in antiviral responses. In line with this notion, we observed that Zac1b was expressed in MEFs infected with Encephalomyocarditis virus (EMCV). We also observed that Zac1-deficient MEFs were less sensitive to EMCV-induced cell death than wild-type MEFs. However, Zac1 gene inactivation had no effect on the survival of mice infected with EMCV. In conclusion, this study describes for the first time a transcriptional regulation of Zac1b, induced by synthetic dsRNA and RNA viruses, the functional significance of which remains to be further investigated. [less ▲]

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See detailLes macrophages interstitiels, gardiens de l'homeostasie immune pulmonaire.
Bedoret, Denis; Bureau, Fabrice ULg; Desmet, Christophe ULg

in Medecine Sciences : M/S (2010), 26(3), 229-31

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See detailIRF3 is required for induction of allergic airway inflammation by dendritic cells
Marichal, Thomas ULg; Bedoret, Denis; Goriely, S et al

Poster (2009)

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See detailIRF3 is required for the induction of allergic airway inflammation by lung dendritic cells in a mouse model of house dust mite-induced atopic asthma
Marichal, Thomas ULg; Bedoret, Denis; Goriely, M. et al

in Abstracts of the 17th Annual European Respiratory Society Congress, Vienna, Austria (2009)

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See detailIRF3 is required for induction of allergic airway inflammation by dendritic cells
Marichal, Thomas ULg; Bedoret, Denis; Goriely, M. et al

Conference (2009)

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See detailLung interstitial macrophages alter dendritic cell functions to prevent airway allergy in mice
Bedoret, Denis ULg; Wallemacq, Hugues ULg; Marichal, Thomas ULg et al

in Journal of Clinical Investigation (2009), 119(12), 3723-38

The respiratory tract is continuously exposed to both innocuous airborne antigens and immunostimulatory molecules of microbial origin, such as LPS. At low concentrations, airborne LPS can induce a lung DC ... [more ▼]

The respiratory tract is continuously exposed to both innocuous airborne antigens and immunostimulatory molecules of microbial origin, such as LPS. At low concentrations, airborne LPS can induce a lung DC-driven Th2 cell response to harmless inhaled antigens, thereby promoting allergic asthma. However, only a small fraction of people exposed to environmental LPS develop allergic asthma. What prevents most people from mounting a lung DC-driven Th2 response upon exposure to LPS is not understood. Here we have shown that lung interstitial macrophages (IMs), a cell population with no previously described in vivo function, prevent induction of a Th2 response in mice challenged with LPS and an experimental harmless airborne antigen. IMs, but not alveolar macrophages, were found to produce high levels of IL-10 and to inhibit LPS-induced maturation and migration of DCs loaded with the experimental harmless airborne antigen in an IL-10-dependent manner. We further demonstrated that specific in vivo elimination of IMs led to overt asthmatic reactions to innocuous airborne antigens inhaled with low doses of LPS. This study has revealed a crucial role for IMs in maintaining immune homeostasis in the respiratory tract and provides an explanation for the paradox that although airborne LPS has the ability to promote the induction of Th2 responses by lung DCs, it does not provoke airway allergy under normal conditions. [less ▲]

Detailed reference viewed: 211 (76 ULg)