Allergin-1 Immunoreceptor Suppresses House Dust Mite-Induced Allergic Th2 Responses

House dust mite (HDM) allergens are leading causes of allergic asthma characterized by T helper 2 (Th2) responses. The lung-resident CD11b dendritic cells (DCs) play a key role in Th2 cell development in HDM-induced allergic asthma. However, the regulatory mechanism of HDM-induced CD11b DC activation remains incompletely understood. Here, we show that mice deficient in an inhibitory immunoreceptor Allergin-1 exacerbated the HDM-induced airway eosinophilia and serum IgE elevation. HDM directly stimulated lung CD11b DCs via the TLR-4-MyD88 pathway and enhanced prostaglandin E2 (PGE2) production that promoted development of Th2 cells. Allergin-1 suppressed the PGE2 production by inhibiting Syk tyrosine kinase activation through recruitment of SHP-1 in HDM-stimulated CD11b DCs, subsequently leading to negative regulation of Th2 responses. These results suggest that Allergin-1 plays an important role in the regulation of HDM-induced allergic asthma.