Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8292622 | Biochemical and Biophysical Research Communications | 2018 | 8 Pages |
Abstract
Patients with DOCK8 deficiency are at increased susceptibility to develop allergic diseases such as food allergy and asthma. Here, we aimed to analyze the pathogenesis of asthma in DOCK8-deficient patients. In our mouse model, DOCK8-knockout (KO) mice sensitized with low-dose OVA were challenged with 1.5% OVA to induce allergic asthma. As compared to that in WT mice, remarkable airway hyperresponsiveness was observed in KO mice. Increased inflammatory cells and eosinophils infiltrated in airway lumen in KO mice especially around bronchi. KO mice showed higher levels of serum IgE and OVA-specific IgE and significantly elevated IgE-producing B cells in blood and in spleen. Surprisingly, nasal administration with rmIL-21 significantly reduced the airway hyperresponsiveness, inflammatory infiltration, as well as the serum IgE and IgE-producing B cells. DOCK8-knockout mice are susceptible to low-dose OVA induced allergic airway inflammation and airway hyperresponsiveness. Supplementary nasal administration of rmIL-21 alleviates allergic asthma in this mouse model.
Keywords
Tyk2AR-HIESGEFscdc2HIESDOCK8IL-21STAT3PBMCsDIDSCIDRac1OVAAllergic asthmaOvalbuminBALFtyrosine kinase 2Ras-related C3 botulinum toxin substrate 1cell division cycle 42peripheral blood mononuclear cellshyper-IgE syndromeGuanine nucleotide exchange factorsBronchoalveolar lavage fluidsignal transducer and activator of transcription 3Dedicator of cytokinesis 8murine model
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Authors
Jiabin Wu, Suqian Zhang, Tao Qin, Jinqiu Jiang, Qiao Liu, Liang Zhang, Xiaodong Zhao, Jihong Dai,