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IL-33 promotes eosinophilia in vivo and antagonizes IL-5-dependent eosinophil hematopoiesis ex vivo

机译:IL-33促进体内嗜曙红细胞增多和拮抗IL-5依赖性嗜酸性粒细胞的造血先体外后体内

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摘要

IL-33 is an IL-1 family cytokine that elicits IL-5-dependent eosinophilia in vivo. We show here that IL-33 promotes minimal eosinophil hematopoiesis via direct interactions with mouse bone marrow progenitors ex vivo and that it antagonizes eosinophil hematopoiesis promoted by IL-5 on SCF and Flt3L primed bone marrow progenitor cells in culture. SCF and Flt3L primed progenitors respond to IL-33 by acquiring an adherent, macrophage-like phenotype, and by releasing macrophage-associated cytokines into the culture medium. IL-33-mediated antagonism of IL-5 was reproduced in part by the addition of GM-CSF and was inhibited by the actions of neutralizing anti-GM-CSF antibody. These findings suggest that the direct actions of IL-33 on bone marrow progenitors primed with SCF and Flt3L are antagonistic to the actions of IL-5 and are mediated in part by GM-CSF.
机译:IL-33是一种IL-1家族细胞因子,可在体内引起依赖IL-5的嗜酸性粒细胞增多。我们在此处显示IL-33通过与离体小鼠骨髓祖细胞的直接相互作用促进最小的嗜酸性粒细胞造血作用,并且它拮抗IL-5对SCF和Flt3L引发的骨髓祖细胞培养物中IL-5促进的嗜酸性粒细胞造血作用。 SCF和Flt3L引发的祖细胞通过获得粘附的巨噬细胞样表型,并将巨噬细胞相关的细胞因子释放到培养基中而对IL-33作出反应。 IL-33介导的IL-5拮抗作用部分地通过添加GM-CSF来再现,并被中和抗GM-CSF抗体的作用所抑制。这些发现表明,IL-33对由SCF和Flt3L引发的骨髓祖细胞的直接作用与IL-5的作用相反,并且部分由GM-CSF介导。

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