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IL‐1β promotes immunoregulatory responses in human blood basophils
Author(s) -
Iype Joseena,
Odermatt Andrea,
Bachmann Sofia,
Coeudevez Mazarine,
Fux Michaela
Publication year - 2021
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.14760
Subject(s) - basophil , immunology , allergic inflammation , interleukin 33 , histamine , immune system , medicine , cytokine , interleukin , inflammation , immunoglobulin e , endocrinology , antibody
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 LCT 4 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.