Dust mites are an important source of allergens. The mechanism by which dust mite allergens induce allergic diseases is to be further investigated. This study aims to elucidate the role of one of the components of dust mite allergens, the Dermatophagoides farinae-8 (Der f 8), in the induction of airway allergy. In this study, the expression of T cell immunoglobulin and mucin domain 4 (TIM4) in dendritic cells (DC) s was analyzed after stimulating with Der f 8 in the culture. The role of Der f 8 in the induction of T helper (Th) 2 inflammation was assessed with an airway allergy mouse model. We observed that, in 34 subtypes of dust mite allergens, Der f 8 uniquely and markedly induced high levels of the TIM4 expression in DCs by modulating the chromatin at the TIM4 promoter locus. Der f 8 played a critical role in the expansion of the Th2 response in the mouse airway via inducing DCs to produce TIM4. Administration with Der f 8-null dust mite extracts (DME) efficiently inhibited the allergic inflammation and induced regulatory T cells in the airway of mice. We conclude that Der f 8 plays an important role in the pathogenesis of dust mite allergy. Vaccination with the Der f 8-null DME is more efficient to inhibit the dust mite allergic inflammation in the airway than the wild DME.