TY - JOUR AU - Conejero, Laura AU - Khouili, Sofía C. AU - Martínez-Cano, Sarai AU - Izquierdo, Helena M. AU - Brandi, Paola AU - Sancho, David T1 - Lung CD103+ dendritic cells restrain allergic airway inflammation through IL-12 production PY - 2017/05/18/ AB - 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. JF - JCI Insight JA - JCI Insight SN - 2379-3708 DO - 10.1172/jci.insight.90420 VL - 2 IS - 10 UR - https://doi.org/10.1172/jci.insight.90420 PB - The American Society for Clinical Investigation ER -