ArtImmune SAS


ArtImmune SAS

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PubMed | Stallergenes Greer, University of Orléans, Artimmune SAS and French Institute of Health and Medical Research
Type: | Journal: Mucosal immunology | Year: 2016

The complement subunit C1q was recently identified as a marker for monocyte-derived regulatory dendritic cells supporting the differentiation of interleukin (IL)-10-secreting CD4

PubMed | Stallergenes Greer, French Institute of Health and Medical Research, Artimmune SAS, University of Orléans and University of Cape Town
Type: | Journal: The Journal of allergy and clinical immunology | Year: 2016

Protein kinase C (PKC) , a serine/threonine kinase, is involved in TWe hypothesized that PKC- contributes to ILC2 activation and might be necessary for ILC2s to instruct the TPRKCQ gene expression was assessed in innate lymphoid cell subsets purified from human PBMCs and mouse lung ILC2s. ILC2 activation and eosinophil recruitment, THere we report that PKC- is expressed in both human and mouse ILC2s. Mice lacking PKC- had reduced ILC2 numbers, TTherefore our findings identify PKC- as a critical factor for ILC2 activation that contributes to T

PubMed | French Institute of Health and Medical Research, Artimmune SAS, University of Orléans, University of Burgundy and Sun Yat Sen University
Type: Journal Article | Journal: Journal of molecular cell biology | Year: 2015

The cysteine protease caspase-1 (Casp-1) contributes to innate immunity through the assembly of NLRP3, NLRC4, AIM2, and NLRP6 inflammasomes. Here we ask whether caspase-1 activation plays a regulatory role in house dust mite (HDM)-induced experimental allergic airway inflammation. We report enhanced airway inflammation in caspase-1-decient mice exposed to HDM with a marked eosinophil recruitment, increased expression of IL-4, IL-5, IL-13, as well as full-length and bioactive IL-33. Furthermore, mice deficient for NLRP3 failed to control eosinophil influx in the airways and displayed augmented Th2 cytokine and chemokine levels, suggesting that the NLPR3 inflammasome complex controls HDM-induced inflammation. IL-33 neutralization by administration of soluble ST2 receptor inhibited the enhanced allergic inflammation, while administration of recombinant IL-33 during challenge phase enhanced allergic inflammation in caspase-1-deficient mice. Therefore, we show that caspase-1, NLRP3, and ASC, but not NLRC4, contribute to the upregulation of allergic lung inflammation. Moreover, we cannot exclude an effect of caspase-11, because caspase-1-deficient mice are deficient for both caspases. Mechanistically, absence of caspase-1 is associated with increased expression of IL-33, uric acid, and spleen tyrosine kinase (Syk) production. This study highlights a critical role of caspase-1 activation and NLPR3/ASC inflammasome complex in the down-modulation of IL-33 in vivo and in vitro, thereby regulating Th2 response in HDM-induced allergic lung inammation.

Besnard A.-G.,French National Center for Scientific Research | Sabat R.,University Hospital Charity | Dumoutier L.,Ludwig Institute for Cancer Research | Dumoutier L.,Catholic University of Leuven | And 14 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2011

Rationale: IL-22 has both proinflammatory and antiinflammatory properties. Its role in allergic lung inflammation has not been explored. Objectives: To investigate the expression and roles of IL-22 in the onset and resolution of experimental allergic asthma and its crosstalk with IL-17A. Methods: IL-22 expression was assessed in patient samples and in the lung of mice immunized and challenged with ovalbumin. IL-22 functions in allergic airway inflammation were evaluated using mice deficient in IL-22 or anti-IL-22 neutralizing antibodies. Moreover, the effects of recombinant IL-22 and IL-17A neutralizing antibodies were investigated. Measurements and Main Results: Increased pulmonary IL-22 expression is found in the serum of patients with asthma and mice immunized and challenged with ovalbumin. Allergic lung inflammation is IL-22 dependent because eosinophil recruitment, Th2 cytokine including IL-13 and IL-33, chemokine production, airway hyperreactivity, and mucus production are drastically reduced in mice deficient in IL-22 or by IL-22 antibody neutralization during immunization of wild-type mice. By contrast, IL-22 neutralization during antigen challenge enhanced allergic lung inflammation with increased Th2 cytokines. Consistent with this, recombinant IL-22 given with allergen challengeprotectsmice from lunginflammation. Finally, IL-22 may regulate the expression and proinflammatory properties of IL-17A in allergic lung inflammation. Conclusions: IL-22 is required for the onset of allergic asthma, but functions as a negative regulator of established allergic inflammation. Our study reveals that IL-22 contributes to the proinflammatory properties of IL-17A in experimental allergic asthma. Copyright © 2011 American Thoracic Society.

Besnard A.-G.,University of Orléans | Besnard A.-G.,French National Center for Scientific Research | Togbe D.,University of Orléans | 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.

Besnard A.-G.,University of Orléans | 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.

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.

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.

Besnard A.-G.,University of Orléans | Togbe D.,University of Orléans | Togbe D.,Artimmune SAS | Couillin I.,University of Orléans | And 7 more authors.
Journal of Molecular Cell Biology | Year: 2012

Allergic asthma has increased dramatically in prevalence and severity over the last three decades. Both clinical and experimental data support an important role of Th2 cell response in the allergic response. Recent investigations revealed that airway exposure to allergen in sensitized individuals causes the release of ATP and uric acid, activating the NLRP3 inflammasome complex and cleaving pro-IL-1β to mature IL-1β through caspase-1. The production of pro-IL-1β requires a toll-like receptor (TLR) 4 signal which is provided by the allergen. IL-1β creates a pro-inflammatory milieu with the production of IL-6 and chemokines which mobilize neutrophils and enhance Th17 cell differentiation in the lung. Here, we review our results showing that NLRP3 inflammasome activation is required to develop allergic airway inflammation in mice and that IL-17 and IL-22 production by Th17 cells plays a critical role in established asthma. Therefore, inflammasome activation leading to IL-1β production contributes to the control of allergic asthma by enhancing Th17 cell differentiation. © The Author (2011).

Background. Thymic stromal lymphopoietin (TSLP) is induced in allergic skin and lung inflammation in man and mice. Methods. Allergic lung inflammation induced by two proteases allergens HDM and papain and a classical allergen ovalbumin was evaluated in vivo in mice deficient for TSLPR. Eosinophil recruitment, Th2 and Th17 cytokine and chemokine levels were determined in bronchoalveolar lavage fluid, lung homogenates and lung mononuclear cells ex vivo. Results. Here we report that mice challenged with house dust mite extract or papain in the absence of TSLPR have a drastic reduction of allergic inflammation with diminished eosinophil recruitment in BAL and lung and reduced mucus overproduction. TSLPR deficient DCs displayed diminished OVA antigen uptake and reduced capacity to activate antigen specific T cells. TSLPR deficient mice had diminished proinflammatory IL-1 , IL-13, and IL-33 chemokines production, while IL-17A, IL-12p40 and IL-10 were increased. Together with impaired Th2 cytokines, IL-17A expressing TCR (+) T cells were increased, while IL-22 expressing CD4(+) T cells were diminished in the lung. Conclusion. Therefore, TSLPR signaling is required for the development of both Th2 and Th22 responses and may restrain IL-17A. TSLP may mediate its effects in part by increasing allergen uptake and processing by DCs resulting in an exacerbated asthma.

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