INTRODUCTION
Allergic asthma is a major and increasingly prevalent chronic inflammatory disease of the airways which is characterized by airway infiltration of eosinophils, Th2 cells, basophils and mast cells, together leading to mucus hypersecretion, airway wall remodeling, and airway hyperresponsiveness1, 2. The most predominant and clearly described endotype of asthma is eosinophilic asthma, which accounts for over 50% of adults with asthma3.
Eosinophils play pivotal roles in allergic airway inflammation, not only working in the effector phase to participate in the inflammation, but also functioning in the early phase to initiate Th2 cell responses, acting as a non-professional antigen-presenting cell (APC)4, 5. Accumulating evidence revealed that eosinophils could express MHCII, migrate to lung and lymph nodes, process the exogenous antigen and induce proliferative Th2 polarization6-8. What drives the process was not elucidated yet.
IL-25, also known as IL-17E, has been shown as a key mediator in allergic asthma, strongly expressed during allergic airway inflammation9. We previously showed that IL-17RA/RB expression on eosinophils of allergic asthmatics was significantly higher than that of atopic non-asthmatics controls and increased significantly 24 h after receiving allergen inhalation challenge10, 11. Although the diverse roles of IL-25 on eosinophils including enhancing survival or reducing apoptosis have been described12, 13, the effect of IL-25 on eosinophils antigen presentation is unknown. With high expression of IL-25 receptors on eosinophils in asthma and the capacity of IL-25 to facilitate classical antigen presentation cell-dendritic cells (DCs) to initiate Th2 responses14-16, we therefore asked whether IL-25 possesses the activity to augment eosinophils to initiate Th2 responses.
Here, we investigated that IL-25 activates the expression of cell surface molecules on eosinophils and antigen uptake by eosinophils. We identify that IL-25 could contribute to eosinophil-mediated Th2 polarization both in ex vivo murine and human studies. In the absence of IL-25, eosinophils chemotaxis to lung during sensitization was hampered, resulting in alleviated airway inflammation and ameliorated Th2 responses.