Anne-Gaelle Besnard

Publications (2)11.08 Total impact

• Article: Inflammasome-IL-1-Th17 response in allergic lung inflammation.

  Anne-Gaelle Besnard, Dieudonnée Togbe, Isabelle Couillin, Zoming Tan, Song Guo Zheng, François Erard, Marc Le Bert, Valérie Quesniaux, Bernhard Ryffel
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  ABSTRACT: 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.
  Journal of Molecular Cell Biology 12/2011; 4(1):3-10.
• Article: Dual Role of IL-22 in allergic airway inflammation and its cross-talk with IL-17A.

  Anne-Gaelle Besnard, Robert Sabat, Laure Dumoutier, Jean-Christophe Renauld, Monique Willart, Bart Lambrecht, Mauro M Teixeira, Sabine Charron, Lizette Fick, François Erard, Katarzyna Warszawska, Kerstin Wolk, Valerie Quesniaux, Bernhard Ryffel, Dieudonnée Togbe
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  ABSTRACT: IL-22 has both proinflammatory and antiinflammatory properties. Its role in allergic lung inflammation has not been explored. To investigate the expression and roles of IL-22 in the onset and resolution of experimental allergic asthma and its cross-talk with IL-17A. 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. 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 challenge protects mice from lung inflammation. Finally, IL-22 may regulate the expression and proinflammatory properties of IL-17A in allergic lung inflammation. 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.
  American Journal of Respiratory and Critical Care Medicine 02/2011; 183(9):1153-63. · 11.08 Impact Factor