House dust mite (HDM) is a major allergen for allergic asthma mediated by T helper 2 (Th2) cells. However, the mechanism underlying HDM-induced Th2 responses remains incompletely understood.
Allergin-1 is an inhibitory immunoreceptor expressed on mast cells (MCs) and inhibited FcεRI-mediated signaling, resulting in suppression of anaphylaxis in mice (Hitomi et al, Nat Immunol., 2010). In this study, we demonstrate that Allegin-1 is also expressed on lung CD11b+ DCs and suppresses HDM-induced DC activation for Th2 responses. Allergin-1-deficient mice showed enhanced HDM-induced allergic airway inflammation and serum titer of IgE. CD11b+ DCs derived from the lung of HDM-administrated Allergin-1-deficient mice expressed higher mRNA levels of prostaglandin E synthase (Ptges) and cyclooxygenase 2 (Cox2), via the TLR4/MyD88 signaling pathway, which mediate PGE2 production. Addition of celecoxib, a selective COX2 inhibitor, in the coculture of HDM-administrated Allergin-1-deficient lung CD11b+ DC with naive CD4+ T cells returned the increased IL-4 to the level in the coculture of WT DC with naive CD4+ T cells. Moreover, transfer of Ptges-knockdowned Allergin-1-deicient DCs into DC-depleted mice showed ameliorated HDM-induced airway inflammation compared with transfer of control shRNA-transduced Allergin-1-deficient DCs. Thus, Allergin-1 suppresses HDM-induced PGE2 production from lung CD11b+ DCs and regulates Th2 responses.