Lung CD103⁺ dendritic cells restrain allergic airway inflammation through IL-12 production

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Abstract

DCs are necessary and sufficient for induction of allergic airway inflammation. CD11b⁺ DCs direct the underlying Th2 immunity, but debate surrounds the function of CD103⁺ DCs in lung immunity and asthma after an allergic challenge. We challenged Batf3^–/– mice, which lacked lung CD103⁺ DCs, with the relevant allergen house dust mite (HDM) as a model to ascertain their role in asthma. We show that acute and chronic HDM exposure leads to defective Th1 immunity in Batf3-deficient mice. In addition, chronic HDM challenge in Batf3^–/– mice results in increased Th2 and Th17 immune responses and exacerbated airway inflammation. Mechanistically, Batf3 absence does not affect induction of Treg or IL-10 production by lung CD4⁺ T cells following acute HDM challenge. Batf3-dependent CD103⁺ migratory DCs are the main source of IL-12p40 in the mediastinal lymph node DC compartment in the steady state. Moreover, CD103⁺ DCs selectively increase their IL-12p40 production upon HDM administration. In vivo IL-12 treatment reverts exacerbated allergic airway inflammation upon chronic HDM challenge in Batf3^–/– mice, restraining Th2 and Th17 responses without triggering Th1 immunity. These results suggest a protective role for lung CD103⁺ DCs to HDM allergic airway inflammation through the production of IL-12.

Authors

Laura Conejero, Sofía C. Khouili, Sarai Martínez-Cano, Helena M. Izquierdo, Paola Brandi, David Sancho