Interleukin 3-induced GITR promotes the activation of human basophils
Interleukin 3-induced GITR promotes the activation of human basophils
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白细胞介素3诱导的GITR促进人嗜碱性粒细胞的活化
DOI：
10.1016/j.cyto.2020.155268
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发表时间：
2020-12-01
期刊：
影响因子：
3.8
通讯作者：
Wang，Hui
中科院分区：
文献类型：
--
作者：
Hong，Li;Tang，Yangyang;Wang，Hui
嗜碱性粒细胞通过分泌组胺、白介素4(IL-4)和白介素13(IL-13)调节变态反应，其主要途径是通过嗜碱性粒细胞表面主要表达的受体FcεRI和IL-3R。IL-3/IL-3R信号轴在调节嗜碱性粒细胞的发育和激活中起关键作用。我们和其他人已经证明，IL-3诱导的表面受体，如ST2，IL-17RB和IL-2受体调节嗜碱性粒细胞的生物学。然而，IL-3诱导的人嗜碱性粒细胞表面蛋白的表达和功能仍有待阐明。在这项研究中，我们的目的是通过对IL-3刺激的嗜碱性粒细胞进行转录分析来确定新的嗜碱性粒细胞激活调节因子。对IL-3处理的嗜碱性粒细胞进行基因表达微阵列分析，发现2050个差异表达基因，其中323个基因编码包括GITR在内的表面蛋白。我们发现GITR主要由IL-3诱导，而不是由抗-IgE、IL-33、fMLP和C5a诱导。针对JAK2、PI3K和MEK1/2的抑制剂可抑制IL-3诱导的GITR。GITR刺激IL-3处理的嗜碱性粒细胞可促进IL-4和IL-13的表达。此外，在IL-3存在的情况下，GITRL可促进IgE介导的脱颗粒。对IL-3激活的嗜碱性粒细胞的转录分析有助于识别新的激活调节因子。IL-3诱导的GITR促进嗜碱性粒细胞的激活，为GITR在Th2相关免疫反应中的重要作用提供了新的证据。
Human basophils regulate allergic reactions by secreting histamine, interleukin 4 (IL-4) and IL-13 through key surface receptors FcεRI as well as IL-3R, which are constitutively expressed on basophils. IL-3/IL-3R signaling axis plays key roles in regulating the development and activation of basophils. We and others have shown that IL-3-induced surface receptors e.g. ST2, IL-17RB and IL-2 receptors regulate the biology of basophils. However, the expression and function of IL-3-induced surface proteins on human basophils remain to be elucidated. We in this study aimed to identify new basophil activation regulators by transcriptomic analysis of IL-3-stimulated basophils. Gene expression microarray analysis of IL-3-treated basophils revealed 2050 differentially expressed genes, of which 323 genes encoded surface proteins including GITR. We identified that GITR was preferentially induced by IL-3 rather than anti-IgE, IL-33, fMLP and C5a. IL-3-induced GITR was suppressed by inhibitors targeting JAK2, PI3K and MEK1/2. Stimulation of IL-3-treated basophils by GITR enhanced the expression of IL-4 and IL-13. Moreover, IgE-mediated degranulation was enhanced by GITRL in the presence of IL-3. This transcriptomic analysis of IL-3-activated basophils helps to identify novel activation regulator. IL-3-induced GITR promoted the activation of basophils, adding new evidence supporting GITR as an important player in Th2-associated immune responses.