Allergen challenge of peripheral blood mononuclear cells from patients with seasonal allergic rhinitis increases IL-17RB, which regulates basophil apoptosis and degranulation
2010 (English)In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 40, no 8, 1194-1202 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2010. Vol. 40, no 8, 1194-1202 p.
apoptosis; basophils; degranulation; gene expression microarray; IL-17RB; seasonal allergic rhinitis
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-98578DOI: 10.1111/j.1365-2222.2010.03542.xISI: 000279650500011PubMedID: 20545698OAI: oai:DiVA.org:liu-98578DiVA: diva2:654995