Abstract
Abstract Allergic asthma is a complex inflammatory disease characterized by airway obstruction and airway hyperresponsiveness. Pulmonary dendritic cells are critical for allergic sensitization as they take up inhaled allergens and direct differentiation of allergen-specific helper T cell lineages in lung-draining lymph nodes. In this study, we used mass cytometry to study lung DC subsets that increase in frequency after allergen inhalation. This approach revealed a novel cell population displaying Ly-6C, in addition to surface markers routinely used to identify type 2 conventional DCs (cDC2), including CD11b and CD26. These Ly-6C+ cells had dendrites, lacked monocyte/macrophage markers such as F4/80 and CD115, and were absent in the mice lacking FMS-like tyrosine kinase 3ligand (FLT3L), a growth factor essential for cDC differentiation. Based on these observations, we conclude that this novel population represents bona fide cDCs. Their numbers in the lung were low at steady state, but increased dramatically after allergic sensitization. Cultured DC precursors (preDCs) displayed Ly-6C, but lost that marker by time. Ly-6C+CD11b+cDCs freshly isolated from mouse lung also lost Ly-6C expression after ex vivo culture. Together, these results suggest that Ly-6C+CD11b+cDCs are the precursor of cDC2. Given that the number of these DCs increase dramatically in the lung after allergen inhalation, they might play important roles in allergic sensitization and the induction of allergic asthma.
Published Version
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