Thymic Stromal Lymphopoietin Enhances Th2/Th22 and Reduces IL-17A in Protease-Allergen-Induced Airways Inflammation.

Abstract

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 β , 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 β (+) 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.