Allergen challenge of peripheral blood mononuclear cells from patients with seasonal allergic rhinitis increases IL-17RB, which regulates basophil apoptosis and degranulation

Abstract

Background: Previously, expression profiling has been used to analyse allergen-challenged T-helper type 2 cells, nasal biopsies and nasal fluid cells from patients with seasonal allergic rhinitis (SAR). Allergen-challenged peripheral blood mononuclear cells (PBMCs) provide a human in vitro model of how antigen-presenting cells, CD4+ T cells and effector cells such as basophils interact in allergic inflammation.

Objective: To identify novel genes and pathways in allergen-challenged PBMCs from patients with SAR using gene expression profiling and functional studies.

Methods: PBMCs from 11 patients with SAR and 23 healthy controls were analysed with gene expression profiling. mRNA expression of IL17RB in basophils was evaluated using quantitative real-time PCR. Membrane protein expression and apoptosis of basophils were examined by flow cytometry. Degranulation of basophils was assessed by measuring beta-hexosaminidase release. Cytokine release was measured using ELISA.

Results: Gene expression microarray analysis of allergen-challenged PBMCs showed that 209 out of 44000 genes were differentially expressed in patients compared with controls. IL17RB was the gene whose expression increased most in patients (P<0.0001). FACS analysis of PBMCs showed, for the first time, that basophils express IL-17RB. Following allergen challenge, IL-17RB protein increased significantly on basophils from patients compared with controls (P<0.05). IL-3 significantly increased both mRNA and protein expressions of IL17RB. Activation of IL-17RB by its ligand, IL-25, inhibited apoptosis of basophils. Moreover, IgE-mediated degranulation was enhanced by IL-25.

Conclusion: Increased expression of IL-17RB on allergen-challenged basophil is regulated by IL-3, inhibits apoptosis and promotes IgE-mediated degranulation of basophils.