Batf3-dependent dendritic cells control house dust mite-driven Th2 and Th17 response through IL-12 production

Abstract

Introduction: Asthma is a chronic inflammatory disease associated to eosinophilia, airway obstruction and airway hyperreactivity. Following inhalation of allergens, conventional lung dendritic cells (DCs), which consist of CD11b + DCs and CD103 + DCs in mice, migrate to the local lymph nodes (LN). Upon exposure to allergens, CD11b + DCs provide the first instruction for T helper cell 2 (Th2) differentiation characteristic in asthma; however, the role of CD103 + DCs in airway inflammation remains controversial. Objectives: Investigate the role of lung CD103 + DCs in HDM-induced asthma. Material and Methods: WT and Batf3 -/- mice, used as a model of CD103 + DC impairment, were chronically exposed to house dust mite (HDM), and the development of characteristic features of asthma was analysed. Results: Batf3-deficient mice show a significant increase in total BAL infiltrates, including mainly an influx of eosinophils and neutrophils. In addition, mice deficient for CD103 + DCs develop more perivascular and peribronchial infiltration than WT mice, which correlates with an increase in Th2 and Th17 cytokine production by lung-draining LN and splenocytes. To further investigate the mechanism, the production of IL-12 by both subsets of lung migratory DCs (CD103 + and CD11b + ) was evaluated in the lung-draining LN following exposure to HDM. Only CD103 + DCs were able to increase the production of IL-12, which in turn enhances Th1 differentiation, attenuating Th2 and Th17 response and main features of asthma. Conclusion: Batf3 -dependent DCs are essential providers of IL-12 that controls induction of Th1 immunity in response to HDM, thus dampening allergic airway inflammation.