Project description:The Gauging Response in Allergic Rhinitis to Sublingual and Subcutaneous Immunotherapy (GRASS) study was a randomized, double-blind, placebo-controlled trial of individuals with timothy grass allergy who received 2 years of placebo, subcutaneous (SCIT), or sublingual immunotherapy (SLIT) and were followed for a total of 3 years. Here we utilized longitudinal transcriptomic profiling of nasal brush and peripheral blood mononuclear cell (PBMC) samples after allergen provocation collected in the GRASS study to uncover airway and systemic expression pathways mediating responsiveness to immunotherapy.
Project description:The Gauging Response in Allergic Rhinitis to Sublingual and Subcutaneous Immunotherapy (GRASS) study was a randomized, double-blind, placebo-controlled trial of individuals with timothy grass allergy who received 2 years of placebo, subcutaneous (SCIT), or sublingual immunotherapy (SLIT) and were followed for a total of 3 years. Here we utilized longitudinal transcriptomic profiling of nasal brush and peripheral blood mononuclear cell (PBMC) samples after allergen provocation collected in the GRASS study to uncover airway and systemic expression pathways mediating responsiveness to immunotherapy.
Project description:Few studies reported for obtaining the grass carp resistant to hemorrhagic disease via gene editing in commercial fish. Here, we demonstrate that the expression and activity of grass carp PI4KB (gcPI4KB) are vital for GCRV-I and GCRV-II replication. Due that obvious cytopathic effect (CPE) in the present available cell lines is only caused by GCRV-I, but GCRV-II is the current popular and fatal strain in grass carp, GCRV-I and GCRV-II are used in cell lines and in grass carp, respectively. The in vitro studies in CIK cells revealed that gcPI4KB interacted with NS80 and VP3 of GCRV-I, and that gcPI4KB was recruited by NS80 for promoting the generation of GCRV VIBs. Since the negative regulatory role of gcPI4KB in GCRV infection was confirmed by in vitro data,we performed gene editing of gcPI4KB in grass carp. We found that PI4KB F0 crispants juvenile grass carp have obvious advantages in promoting growth and in resisting GCRV-II infection. Compared with uninfected WT grass carp, the uninfected PI4KB F0 crispants juvenile grass carp exhibit a higher expression level of many genes involved in growth- and development-related metabolic pathways such as the FoxO signaling pathway and insulin signaling pathway. Compared with WT grass carp without infection, PI4KB F0 crispants juvenile grass carp without infection or WT grass carp infected with GCRV-II, higher expression levels for many genes involved in metabolic diseases and viral infection were observed in the liver from PI4KB F0 crispants juvenile grass carp infected with GCRV-II. Altogether, the present study suggests the mechanism of gcPI4KB in facilitating GCRV replication, the signaling pathways regulated by gcPI4KB, and the possibility to obtain the grass carp resistant to hemorrhagic disease via gene editing of PI4KB.
