DCIR is an Important Regulatory Molecule in Allergic Inflammation

Abstract

Abstract The dendritic cell immunoreceptor (DCIR) is an inhibitory C-type lection receptor possessing immunoregulatory properties. We have shown that DCIR serves as a receptor for IVIg. In this study, we sought to determine its requirement in modulating IVIg mechanism of action by using a murine model of allergic of airways disease. Wild type (WT) and DCIR−/− mice were sensitized and challenged with ovalbumin (OVA), and lung histopathology, bronchoalveolar lavage and phenotyping of inflammatory cells were performed. We further studied the effect of IVIg on allergen uptake and processing of CD11c+ cells in vitro. Briefly, bone marrow-derived dendritic cells from WT, DCIR−/− and Fcr2b−/− mice were treated with IVIg prior to exposure to OVA-ALEXA-647 or DQ-OVA. DCIR−/− mice exhibit exacerbated pulmonary inflammation and eosinophilia compared to WT mice; this phenotype is rescued by IVIg treatment as in WT mice. Furthermore, IVIg significantly impairs the antigen uptake and processing machinery of dendritic cells from WT and DCIR−/− derived BMDCs but not that of Fcr2b−/−-derived BMDCs. In conclusion, DCIR is important in regulating allergic airway inflammation and its presence is not essential for IVIg to function. DCIR appears to be required for normal regulation of pulmonary inflammation.