IL-1β promotes immunoregulatory responses in human blood basophils.

Iype, Joseena; Odermatt, Andrea; Bachmann, Sofia; Coeudevez, Mazarine; Fux, Michaela (2021). IL-1β promotes immunoregulatory responses in human blood basophils. Allergy, 76(7), pp. 2017-2029. Wiley 10.1111/all.14760

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Human basophils are essential effector cells of chronic allergic inflammation. IL-1 family cytokines such as interleukin (IL)-33 and IL-1β 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-1β on the function of basophils has not been well investigated. Here, we elucidate whether IL-1β regulates the function of human basophils and compared the effects of IL-1β and IL-33 on basophils of healthy and allergic subjects. We found that IL-1β activates the p38 MAPK signaling pathway and promotes IL-8 release in basophils of healthy donors, while FcεRI-mediated LCT4 and histamine secretion is not affected. Strikingly, in the presence of IL-3, IL-1β shows more potency than IL-33, as evidenced by the enhanced p38 phosphorylation and NF-κB 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-1β 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-1β in allergic subjects compared to those from healthy controls.

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