Uridine diphosphate-glucose/P2Y14R axis is a nonchemokine pathway that selectively promotes eosinophil accumulation

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 P2Y(14)R in amplifying eosinophil accumulation in the lung. During type 2 inflammation, UDP-G activates P2Y(14)R on eosinophils, inducing the cells to move and migrate into the lung. Pharmacologically or genetically inhibiting P2Y(14)R on eosinophils attenuated eosinophil infiltration and AHR. Future experiments, including identifying additional type 2 factors regulating P2Y(14)R expression on lung eosinophils, are necessary to ascertain the impact of targeting P2Y(14)R as an alternative or adjunctive therapy to current type 2 biologics for the treatment of asthma.

Automated summary

Allergic asthma is characterized by dysregulated type 2 immune responses, including degranulating airway eosinophils that induce tissue damage and airway hyperresponsiveness. A study identified a mechanism involving UDP-glucose and P2Y(14)R in amplifying eosinophil accumulation in the lung, suggesting potential as an alternative therapy for asthma. By targeting P2Y(14)R, eosinophil infiltration and AHR can be attenuated, providing a promising approach for asthma treatment.