Interleukin 3-induced GITR promotes the activation of human basophils. (December 2020)

• Record Type: Journal Article
• Authors: Hong, Li; Tang, Yangyang; Pan, Shuai; Xu, Meizhen; Shi, Yanbiao; Gao, Sijia; Sui, Chao; He, Cheng; Zheng, KuiYang; Tang, Renxian; Shi, Zhixu; Wang, Qingling; Wang, Hui
• Is Part Of: Cytokine. Volume 136(2020)
• Publication Date: 2020-12
• Subjects: Basophil -- GITR -- IL-4 -- IL-13 -- Degranulation; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2020.155268
• Languages: English
• ISSNs: 1043-4666

Abstract

Highlights: IL-3 induced 323 genes encoding surface proteins on human basophils. GITR was preferentially induced on basophils by IL-3. GITR promoted secretion of histamine, IL-4 and IL-13 by IL-3-activated basophils. Abstract: 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.