Critical role of the Fc receptor gamma-chain on APCs in the development of allergen-induced airway hyperresponsiveness and inflammation

The FeR common y-chain (FcRy) is an essential component of the receptors Fe epsilon RI, Fc gamma RI, and Fc gamma RIII, which are expressed on many inflammatory cell types. The role of these receptors in the initiation or maintenance of allergic inflammation has not been well defined. FcR gamma-deficient (FcRy(-/-)) and control (wild-type (WT)), mice were sensitized and subsequently challenged with OVA. Following sensitization and challenge to OVA, FeRy-deficient (FcRy(-/-)) mice developed comparable levels of IgE and IgG1 as WT mice. However, numbers of eosinophils, levels of IL-5, IL-13, and eotaxin in bronchoalveolar lavage fluid, and mononuclear cell (MNC) proliferative responses to OVA were significantly reduced, as was airway hyperresponsiveness (AHR) to inhaled methacholine. Reconstitution of FeRy(-/-) mice with whole spleen MNC from WT mice before sensitization restored development of AHR and the numbers of eosinophils in bronchoalveolar lavage fluid; reconstitution after sensitization but before OVA challenge only partially restored these responses. These responses were also restored when FcRy(-/-) mice received T cell-depleted MNC, T and B cell-depleted MNC, or bone marrow-derived dendritic cells before sensitization from FcR(+/+) or Fe gamma RIII-deficient but not FcRy(-/-) mice. The expression levels of Fc gamma RIV on bone marrow-derived dendritic cells from FcR(+/+) mice were found to be low. These results demonstrate that expression of FcR gamma, most likely Fc gamma RI, on APCs is important during the sensitization phase for the development of allergic airway inflammation and AHR.