Il-1 Beta Promotes Immunoregulatory Responses In Human Blood Basophils

Human basophils are essential effector cells of chronic allergic inflammation. IL-1 family cytokines such as interleukin (IL)-33 and IL-1 beta are elevated in serum and bronchoalveolar lavage fluid of allergic asthmatics. IL-33 is known to be a critical regulator of basophil's T2 immune responses. However, the effect of IL-1 beta on the function of basophils has not been well investigated. Here, we elucidate whether IL-1 beta regulates the function of human basophils and compared the effects of IL-1 beta and IL-33 on basophils of healthy and allergic subjects. We found that IL-1 beta activates the p38 MAPK signaling pathway and promotes IL-8 release in basophils of healthy donors, while Fc epsilon RI-mediated LCT(4)and histamine secretion is not affected. Strikingly, in the presence of IL-3, IL-1 beta shows more potency than IL-33, as evidenced by the enhanced p38 phosphorylation and NF-kappa B activation, as well as the release of both IL-13 and IL-8. We found that the enhanced basophil responsiveness is achieved through IL-3-induced IL-1RI surface expression. Importantly, basophils of allergic donors release significantly higher amounts of IL-8 compared to those from healthy donors upon IL-33 and IL-1 beta stimulation. Consistently, we detected increased IL-1RI and decreased IL-3 receptor alpha-chain (CD123) and CCR3 expression on basophils of allergic subjects compared to healthy controls, suggesting an in vivo IL-3 priming in allergic donors. In summary, our results suggest enhanced sensitivity of basophils toward IL-33 and IL-1 beta in allergic subjects compared to those from healthy controls.