2. Academic Validation
  3. Interleukin 3-induced GITR promotes the activation of human basophils

Interleukin 3-induced GITR promotes the activation of human basophils

  • Cytokine. 2020 Dec;136:155268. doi: 10.1016/j.cyto.2020.155268.
Li Hong 1,  Yangyang Tang 2,  Shuai Pan 1,  Meizhen Xu 1,  Yanbiao Shi 1,  Sijia Gao 1,  Chao Sui 1,  Cheng He 1,  KuiYang Zheng 1,  Renxian Tang 1,  Zhixu Shi 3,  Qingling Wang 2,  Hui Wang 4
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; National Experimental Demonstration Center for Basic Medicine Education, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.
  • 2 Department of Pathology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.
  • 3 Xuzhou Red Cross Blood Center, Xuzhou, Jiangsu 221400, China.
  • 4 Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; National Experimental Demonstration Center for Basic Medicine Education, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China. Electronic address: hui.wang@xzhmu.edu.cn.
PMID: 32889153 DOI: 10.1016/j.cyto.2020.155268
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.

Keywords

Basophil; Degranulation; GITR; IL-13; IL-4.

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