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


CONCLUSIONS
Increased expression of IL-17RB on allergen-challenged basophil is regulated by IL-3, inhibits apoptosis and promotes IgE-mediated degranulation of basophils.
Wang
H
H
The Unit for Clinical Systems Biology, Department of Microbiology and Immunology, Mucosal Immunobiology and Vaccine Research Center, Sahlgrenska Academy, University of Gothenburg, and The Pediatric Allergy Unit, The Queen Silvia Children's Hospital, Gothenburg, Sweden. hui.wang@gu.se
Mobini
R
R
Fang
Y
Y
Barrenäs
F
F
Zhang
H
H
Xiang
Z
Z
Benson
M
M
D000485:Allergens / Q000276:immunology / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology; D001491:Basophils / Q000276:immunology / Q000378:metabolism*; D015550:Cell Degranulation / Q000235:genetics / Q000276:immunology*; D002469:Cell Separation; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis; D053722:Receptors, Interleukin-17 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D006255:Rhinitis, Allergic, Seasonal / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*
D000485:Allergens; D012333:RNA, Messenger; D053722:Receptors, Interleukin-17