FcRγ- and IL-33-dependent house dust mite extract antigen-uptake in lung antigen presenting cells (HYP4P.311)

Abstract

Abstract Allergic sensitization can be generated against various allergens, leading to Th2-mediated inflammation and subsequent asthmatic symptoms. However, the exact mechanisms behind allergic sensitization are not precisely understood. Our previous work demonstrated that house dust mite (HDM) signals through the FcRγ-associated receptor Dectin-2 and induces expression of IL-33 by DCs, leading to the differentiation of Th2 cells and asthma pathogenesis. Here, we sought to determine whether changes in antigen uptake by immune cells in the lung interstitium may be responsible for the diminished inflammation in response to HDM previously demonstrated in FcRγ- and IL-33-knockout mice. To this end, we evaluated antigen uptake in lung APC subsets 18 hours after intratracheal instillation of fluorescently labeled HDM in FcRγ- and IL-33-knockout mice. Our findings demonstrate the uptake of HDM by fewer lung-interstitial Ly6C+ monocytes in FcRγ-deficient mice, but equal uptake by DC subsets. Surprisingly, a defect in IL-33 alone resulted in reduced numbers of Ly6C+ monocytes, moDCs, and CD11b+ cDCs containing HDM in the lung interstitium. These data suggest a mechanism by which an FcRγ-dependent receptor is required for uptake of HDM by lung-interstitial Ly6C+ monocytes in order to upregulate IL-33 production in the lung, which may promote uptake by other APC subsets and induce Th2-mediated allergic airway inflammation.