title: Suppression of dust mite allergy by mucosal delivery of a hypoallergenic derivative in a mouse model.
abstract: Allergic asthma caused by house dust mite (HDM) is becoming a public health problem. Specific immunotherapy is considered to be the only curative treatment, but it is always associated with IgE-mediated side effects in the therapy process. A few studies showed that the disruption of allergen IgE epitopes could reduce IgE reactivity and thus reduce allergenic activity. In this study, a hypoallergenic derivative of the major HDM allergen Der p2 was constructed by genetic engineering. This derivative was confirmed to have a considerably reduced IgE reactivity compared with Der p2. For its application in vivo, recombinant Lactococcus lactis (LL-DM) was engineered to deliver the Der p2 derivative to the intestinal mucosal surface. Oral administration of LL-DM significantly alleviated Der p2-induced airway inflammation, as shown by reduced inflammatory infiltration and a reduction in Th2 cytokines in bronchoalveolar lavage. This protective effect was associated with an up-regulation of specific IgG2a and a decrease in IL-4 level in the spleen which may affect specific IgE response. Moreover, the levels of regulatory T cells in the mesenteric lymph nodes and spleen were markedly increased in mice fed with LL-DM, suggesting that LL-DM can inhibit allergic responses via the induction of regulatory T cell. Our results indicate that the Der p2 derivative is a promising therapeutic molecule for specific immunotherapy and recombinant lactic acid bacteria could be developed as a promising treatment or prevention strategy for allergic diseases.
authors: State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, 214122, People's Republic of China.
authors: Chunqing
authors: C
authors: Ai
authors: Qiuxiang
authors: Q
authors: Zhang
authors: Junrong
authors: J
authors: Ding
authors: Chengcheng
authors: C
authors: Ren
authors: Gang
authors: G
authors: Wang
authors: Xiaoming
authors: X
authors: Liu
authors: Fengwei
authors: F
authors: Tian
authors: Jianxin
authors: J
authors: Zhao
authors: Hao
authors: H
authors: Zhang
authors: Yong Q
authors: YQ
authors: Chen
authors: Wei
authors: W
authors: Chen
mesh_terms: D000818:Animals; D039741:Antigens, Dermatophagoides / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D060829:Arthropod Proteins / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D007167:Immunotherapy; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D039981:Pyroglyphidae / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
chemical_list: D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; C451163:Dermatophagoides pteronyssinus antigen p 2; D015847:Interleukin-4