LSC Abstract – Batf3-dependent dendritic cells control exacerbated allergic airways inflammation to house dust mite (HDM)

Abstract

Background: Asthma is a chronic inflammatory disease associated to eosinophilia, with variable and often reversible airway obstruction accompanied by airway hyperreactivity. Following inhalation of allergens, conventional lung dendritic cells (DCs), which consist of CD11b + and CD103 + DCs in mice, migrate to the local lymph nodes (LN). It has been suggested that upon exposure to allergens, CD11b + DCs interact with naive T cells in the lung-draining LN, providing the first instruction for T helper cell 2 (Th2) differentiation characteristic in asthma; however, the role of CD103 + DCs in airway inflammation remains controversial. Aim: Investigate the role of lung CD103 + DCs in HDM-induced asthma. Methods: WT and Batf3 -/- mice, used as a model of CD103 + DC impairment, were exposed to HDM, and the development features of asthma such as increase in BAL infiltrates, Th2 and Th17 cytokine production, mucus secretion and IgE levels in sera analysed. Results: Batf3-deficient mice show a significant increase in total BAL infiltrates. 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. To further investigate the mechanism, the production of IL-12 by lung migratory DCs was evaluated in the lung-draining LN following exposure to HDM. Only CD103 + DCs were able to induce 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.