https://nova.newcastle.edu.au/vital/access/ /manager/Index en-au 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:4425 Wed 11 Apr 2018 13:44:07 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:43941 Wed 05 Oct 2022 12:51:59 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:46635 JCI, Karcz et al. identified a mechanism involving the nucleotide sugar UDP-glucose (UDP-G) and the purinergic receptor P2Y₁₄R in amplifying eosinophil accumulation in the lung. During type 2 inflammation, UDP-G activates P2Y₁₄R on eosinophils, inducing the cells to move and migrate into the lung. Pharmacologically or genetically inhibiting P2Y₁₄R on eosinophils attenuated eosinophil infiltration and AHR. Future experiments, including identifying additional type 2 factors regulating P2Y₁₄R expression on lung eosinophils, are necessary to ascertain the impact of targeting P2Y₁₄R as an alternative or adjunctive therapy to current type 2 biologics for the treatment of asthma.]]> Tue 29 Nov 2022 10:35:15 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:1061 Sat 24 Mar 2018 08:32:13 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:2202 Sat 24 Mar 2018 08:30:10 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:17727 − ion conductance). Pharmacological analyses in vitro and in vivo determined that elevated Cl⁻ conductance is mediated by altered cystic fibrosis transmembrane conductance regulator expression and activity. Generation of iIL-13Tg/Il13rα1^−/−, iIL-13Tg/Il13rα2^−/−, and iIL-13Tg/Stat6^−/− mice revealed that IL-13-mediated dysregulation of epithelial architecture and Cl⁻ conductance is dependent on IL-13Rα1 and STAT-6. These observations demonstrate a central role for the IL-13/IL-13Rα1 pathway in the regulation of intestinal epithelial cell Cl⁻ secretion via up-regulation of cystic fibrosis transmembrane conductance regulator, suggesting an important role for this pathway in secretory diarrhea.]]> Sat 24 Mar 2018 07:57:45 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:6617 Sat 24 Mar 2018 07:46:21 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:33088 H2 cells), their associated cytokines, and eosinophils in the regulation of hallmark features of allergic asthma. Notably, we consider the complexity of type-2 responses and studies that have explored integrated signaling among classical T_H2 cytokines (IL-4, IL-5, and IL-13), which together with CCL11 (eotaxin-1) regulate critical aspects of eosinophil recruitment, allergic inflammation, and airway hyper-responsiveness (AHR). Among our most important findings, we have provided evidence that the initiation of T_H2 responses is regulated by airway epithelial cell-derived factors, including TRAIL and MID1, which promote T_H2 cell development via STAT6-dependent pathways. Further, we highlight studies demonstrating that microRNAs are key regulators of allergic inflammation and potential targets for anti-inflammatory therapy. On the background of T_H2 inflammation, we have demonstrated that innate immune cells (notably, airway macrophages) play essential roles in the generation of steroid-resistant inflammation and AHR secondary to allergen- and pathogen-induced exacerbations. Our work clearly indicates that understanding the diversity and spatiotemporal role of the inflammatory response and its interactions with resident airway cells is critical to advancing knowledge on asthma pathogenesis and the development of new therapeutic approaches.]]> Fri 24 Aug 2018 16:27:29 AEST ]]>