School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, and Hunter Medical Research Institute (HMRI), Newcastle, New South Wales, Australia.
Mary H. Weiser Food Allergy Center, Department of Pathology, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA.
J Clin Invest. 2021 Apr 1;131(7). doi: 10.1172/JCI147735.
Allergic asthma is a chronic inflammatory airway disease characterized by dysregulated type 2 immune responses, including degranulating airway eosinophils that induce tissue damage and airway hyperresponsiveness (AHR). The type 2 cytokines interleukin 5 (IL-5) and IL-13 and the eosinophil-specific chemokine CCL11/CCL24/CCL26 axis recruit, activate, and regulate eosinophils in the airways. In this issue of the 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.
变应性哮喘是一种慢性炎症性气道疾病，其特征是 2 型免疫反应失调，包括脱颗粒的气道嗜酸性粒细胞，诱导组织损伤和气道高反应性（AHR）。2 型细胞因子白细胞介素 5（IL-5）和 IL-13 以及嗜酸性粒细胞特异性趋化因子 CCL11/CCL24/CCL26 轴招募、激活和调节气道中的嗜酸性粒细胞。在本期 JCI 中，Karcz 等人确定了一种涉及核苷酸糖 UDP-葡萄糖（UDP-G）和嘌呤能受体 P2Y14R 的机制，该机制可放大肺部嗜酸性粒细胞的积累。在 2 型炎症中，UDP-G 激活嗜酸性粒细胞上的 P2Y14R，诱导细胞移动并迁移到肺部。在嗜酸性粒细胞上药理学或基因抑制 P2Y14R 可减弱嗜酸性粒细胞浸润和 AHR。未来的实验，包括确定调节肺嗜酸性粒细胞上 P2Y14R 表达的其他 2 型因子，对于确定将 P2Y14R 作为当前 2 型生物制剂治疗哮喘的替代或辅助疗法的影响是必要的。
