Allergen-Induced Increases in Interleukin-25 and Interleukin-25 Receptor Expression in Mature Eosinophils from Atopic Asthmatics.
BACKGROUND
Interleukin (IL)-25 plays a pivotal role in type 2 immune responses. In a baseline cross-sectional study, we previously showed that IL-25 plasma levels and IL-25 receptor (IL-25R: IL-17RA, IL-17RB, and IL-17RA/RB) expression on mature blood eosinophils are increased in atopic asthmatics compared to normal nonatopic controls. This study investigated allergen-induced changes in IL-25 and IL-25R expression in eosinophils from asthmatics.


METHODS
Dual responder atopic asthmatics (n = 14) were enrolled in this randomized diluent-controlled crossover allergen challenge study. Blood was collected before and 24 h after the challenge. The surface expression of IL-25R was evaluated by flow cytometry on eosinophils and Th2 memory cells. In addition, plasma levels of IL-25 were measured by ELISA, and functional responses to IL-25 including type 2 cytokine expression, degranulation, and the migrational responsiveness of eosinophils were evaluated in vitro.


RESULTS
Following the allergen but not the diluent inhalation challenge, significant increases in the expression of IL-17RB and IL-17RA/B were found on eosinophils but not on Th2 memory cells. IL-25 plasma levels and the number of eosinophils but not of Th2 memory cells expressing intracellular IL-25 increased significantly in response to the allergen but not the diluent challenge. Stimulation with physiologically relevant concentrations of IL-25 in vitro caused (i) degranulation of eosinophils (measured by eosinophil peroxidase release), (ii) enhanced intracellular expression of IL-5 and IL-13, and (iii) priming of eosinophil migration to eotaxin. IL-25 stimulated intracellular cytokine expression, and the migration of eosinophils was blocked in the presence of a neutralizing IL-25 antibody.


CONCLUSIONS
Our findings suggest that the IL-25/IL-25R axis may play an important role in promoting the recruitment and proinflammatory function of eosinophils in allergic asthma.
Division of Respirology, Department of Medicine, McMaster University, Hamilton, Ont., Canada.
Wei
W
Tang
Steven G
SG
Smith
Brittany
B
Salter
John Paul
JP
Oliveria
Patrick
P
Mitchell
Graeme M
GM
Nusca
Karen
K
Howie
Gail M
GM
Gauvreau
Paul M
PM
O'Byrne
Roma
R
Sehmi
D000328:Adult; D000485:Allergens / Q000276:immunology*; D001249:Asthma / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism*; D015415:Biomarkers; D015550:Cell Degranulation / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D047209:Eosinophil Peroxidase / Q000378:metabolism; D004804:Eosinophils / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism*; D007150:Immunohistochemistry; D020381:Interleukin-17 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018123:Receptors, Interleukin / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D012129:Respiratory Function Tests; D055815:Young Adult
D000485:Allergens; D015415:Biomarkers; D016207:Cytokines; C560912:IL-25 receptor protein, human; C486701:IL25 protein, human; D020381:Interleukin-17; D018123:Receptors, Interleukin; D047209:Eosinophil Peroxidase