FcγRIII signaling promotes IL-33-dependent monocyte migration to the lung extravascular space.

Abstract

Abstract IL-33 is implicated in type 2 inflammatory processes, including allergic asthma. Our group previously demonstrated that two Th2 stimuli, allergen-specific IgG immune complexes (ICs) and house dust mite extract (HDM), signal through FcRγ-associated receptors on antigen presenting cells to upregulate IL-33 and induce type 2 allergic airway inflammation. In this study, we find that monocytes from WT, but not IL-33−/− or FcγRIII−/− mice, accumulate in the lung extravascular space within 18 hours of OVA-IC challenge. Exogenous IL-33 treatment in the airways is sufficient to restore monocyte accumulation in the IL-33−/− mice. Further, treatment with pertussis toxin abolishes IL-33-dependent monocyte accumulation, a finding consistent with GPCR-dependent migration of these cells. Our findings suggest that during allergic sensitization, activation of the FcRγ signaling pathway promotes IL-33- and GPCR-dependent monocyte migration to the lung extravascular space, where monocytes may then contribute to type 2 allergic inflammation.