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Besnard A.-G.,University of Orleans | Besnard A.-G.,French National Center for Scientific Research | Togbe D.,University of Orleans | Togbe D.,French National Center for Scientific Research | And 9 more authors.
European Journal of Immunology | Year: 2011

IL-33, a new member of the IL-1 family cytokine, is involved in Th2-type responses in a wide range of diseases and signals through the ST2 receptor expressed on many immune cells. Since the effects of IL-33 on DCs remain controversial, we investigated the ability of IL-33 to modulate DC functions in vitro and in vivo. Here, we report that IL-33 activates myeloid DCs to produce IL-6, IL-1b, TNF, CCL17 and to express high levels of CD40, CD80 OX40L and CCR7. Importantly, IL-33-activated DCs prime naive lymphocytes to produce the Th2 cytokines IL-5 and IL-13, but not IL-4. In vivo, IL-33 exposure induces DC recruitment and activation in the lung. Using an OVA-induced allergic lung inflammation model, we demonstrate that the reduced airway inflammation in ST2-deficient mice correlates with the failure in DC activation and migration to the draining LN. Finally, we show that adoptive transfer of IL-33-activated DCs exacerbates lung inflammation in a DC-driven model of allergic airway inflammation. These data demonstrate for the first time that IL-33 activates DCs during antigen presentation and thereby drives a Th2-type response in allergic lung inflammation. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source


Madouri F.,French National Center for Scientific Research | Quesniaux V.,French National Center for Scientific Research | Ryffel B.,French National Center for Scientific Research | Togbe D.,French National Center for Scientific Research | Togbe D.,ArtImmune SAS
Revue Francaise d'Allergologie | Year: 2013

Allergic asthma is in clear expansion in industrialized countries, increasing both in prevalence and severity. The mechanisms of sensitization and the triggering of asthma are complex. This disease is associated with a Th2-cell immune response in which IL-4, IL-13, IgE, IL-5 and thymic stromal lymphopoetin (TSLP) are involved. A Th17 component, which secretes IL-17 and IL-22, has likewise been linked to allergic asthma. TSLP is a type 1 cytokine associated with the cellular and molecular mechanisms of allergic asthma. In this review, we will summarize the functions of TSLP on various cell types and its role in allergies, giving particular attention to cells producing IL-17 and IL-22 in allergic asthma. © 2013 Elsevier Masson SAS. Source


Guabiraba R.,University of Glasgow | Guabiraba R.,French National Center for Scientific Research | Ryffel B.,French National Center for Scientific Research | Ryffel B.,UCT | Ryffel B.,ArtImmune SAS
Immunology | Year: 2014

Dengue viruses (DENV), a group of four serologically distinct but related flaviviruses, are responsible for one of the most important emerging viral diseases. This mosquito-borne disease has a great impact in tropical and subtropical areas of the world in terms of illness, mortality and economic costs, mainly due to the lack of approved vaccine or antiviral drugs. Infections with one of the four serotypes of DENV (DENV-1-4) result in symptoms ranging from an acute, self-limiting febrile illness, dengue fever, to severe dengue haemorrhagic fever or dengue shock syndrome. We reviewed the existing mouse models of infection, including the DENV-2-adapted strain P23085. The role of CC chemokines, interleukin-17 (IL-17), IL-22 and invariant natural killer T cells in mediating the exacerbation of disease in immune-competent mice is highlighted. Investigations in both immune-deficient and immune-competent mouse models of DENV infection may help to identify key host-pathogen factors and devise novel therapies to restrain the systemic and local inflammatory responses associated with severe DENV infection. © 2013 John Wiley & Sons Ltd. Source


Besnard A.-G.,French National Center for Scientific Research | Guillou N.,French National Center for Scientific Research | Tschopp J.,University of Lausanne | Erard F.,French National Center for Scientific Research | And 6 more authors.
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2011

Background: Inflammasome activation with the production of IL-1β received substantial attention recently in inflammatory diseases. However, the role of inflammasome in the pathogenesis of asthma is not clear. Using an adjuvant-free model of allergic lung inflammation induced by ovalbumin (OVA), we investigated the role of NLRP3 inflammasome and related it to IL-1R1 signaling pathway. Methods: Allergic lung inflammation induced by OVA was evaluated in vivo in mice deficient in NLRP3 inflammasome, IL-1R1, IL-1β or IL-1α. Eosinophil recruitment, Th2 cytokine, and chemokine levels were determined in bronchoalveolar lavage fluid, lung homogenates, and mediastinal lymph node cells ex vivo. Results: Allergic airway inflammation depends on NLRP3 inflammasome activation. Dendritic cell recruitment into lymph nodes, Th2 lymphocyte activation in the lung and secretion of Th2 cytokines and chemokines are reduced in the absence of NLRP3. Absence of NLRP3 and IL-1β is associated with reduced expression of other proinflammatory cytokines such as IL-5, IL-13, IL-33, and thymic stromal lymphopoietin. Furthermore, the critical role of IL-1R1 signaling in allergic inflammation is confirmed in IL-1R1-, IL-1β-, and IL-1α-deficient mice. Conclusion: NLRP3 inflammasome activation leading to IL-1 production is critical for the induction of a Th2 inflammatory allergic response. © 2011 John Wiley & Sons A/S. Source


Besnard A.-G.,University of Orleans | Besnard A.-G.,University of Cape Town | Struyf S.,University of Glasgow | Guabiraba R.,University of Cape Town | And 9 more authors.
Journal of Leukocyte Biology | Year: 2013

IPF is a chronic, progressive pulmonary disease, leading to respiratory failure. In search of mechanisms of IPF, we used the bleomycin-induced lung-injury model in mice, which causes acute inflammation that may progress to chronic lung inflammation and fibrosis. Here, we asked whether CXCL6/GCP-2, a member of the CXC chemokine superfamily, may be involved in IPF development. First, we reported an increase of CXCL6 levels in BALF from patients with IPF, as well as in the lung of mice, 24 h after bleomycin administration. To investigate whether CXCL6 played a role in experimental bleomycin-induced pulmonary fibrosis, we treated mice with an anti-mCXCL6 mAb that has been shown to inhibit neutrophil chemotaxis in vitro. CXCL6 antibody blockade attenuated acute inflammation with a reduced pulmonary neutrophil influx, IL-1Β, CXCL1, and TIMP-1 production. In the later phase (14 days after bleomycin exposure), lymphocyte recruitment and fibrosis markers, such as collagen and TIMP-1, were diminished, as well as collagen deposition and fibrotic lesion the lung. Therefore, the data suggest that CXCL6 contributes to experimental pulmonary fibrosis, and CXCL6 inhibition might be used to reduce lung toxicity associated with bleomycin treatment. J. Leukoc. Biol. 94: 1317-1323; 2013. © Society for Leukocyte Biology. Source

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