%0 Journal Article
%T Thymic Stromal Lymphopoietin Enhances Th2/Th22 and Reduces IL-17A in Protease-Allergen-Induced Airways Inflammation
%A Dieudonn¨¦e Togbe
%A Louis Fauconnier
%A Fahima Madouri
%A Tiffany Marchiol
%A Pauline Chenuet
%A Nathalie Rouxel
%A Aur¨¦lie Ledru
%A Fran£¿ois Erard
%A Valerie Quesniaux
%A Bernhard Ryffel
%J ISRN Allergy
%D 2013
%R 10.1155/2013/971036
%X 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¦Â, 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¦Â+ 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. 1. Introduction The allergic inflammatory response is characterized by a predominant Th2-cell pathway, which is initiated by the uptake of allergens by professional antigen presenting cells (APCs) that present selected peptides on MHC class II molecules to naive T cells, together with isotype switching of B cells to generate IgE antibodies specific for common environmental allergens [1]. The cytokines associated with Th2 response are IL-4, IL-5, IL-9, IL-13, and IL-33 [2, 3]. Thymic stromal lymphopoietin (TSLP) was first identified as a growth-promoting factor produced by mouse thymic stromal cells that supported the development of immature B cells to the B220+/IgM+ stage [4]. TSLP is a type I cytokine that acts via the heteromeric receptor consisting of IL-7R¦Á and a TSLP-specific subunit, TSLP receptor (TSLPR) [5, 6] signaling via JAK1 and JAK2 to mediate the activation of STAT5A and STAT5B [7]. TSLPR has homology to the common cytokine receptor -chain, , a component of the receptors for IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21 [8]. TSLP is expressed by a range of cell types, including epithelial cells, fibroblasts, keratinocytes, mast cells, protease-activated basophils, human CD68+ macrophages, and
%U http://www.hindawi.com/journals/isrn.allergy/2013/971036/