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

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. Batf3dependent 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.