Interleukin 3-induced GITR promotes the activation of human basophils

Cytokine. 2020 Dec:136:155268. doi: 10.1016/j.cyto.2020.155268. Epub 2020 Sep 2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basophils / immunology*
  • Extracellular Signal-Regulated MAP Kinases / immunology
  • Female
  • Gene Expression Regulation / immunology*
  • Glucocorticoid-Induced TNFR-Related Protein / immunology*
  • Humans
  • Interleukin-3 / immunology*
  • MAP Kinase Signaling System / immunology*
  • Male

Substances

  • Glucocorticoid-Induced TNFR-Related Protein
  • IL3 protein, human
  • Interleukin-3
  • TNFRSF18 protein, human
  • Extracellular Signal-Regulated MAP Kinases