Airway wall expression of OX40/OX40L and interleukin-4 in asthma.
BACKGROUND
The costimulatory molecule OX40 and its ligand, OX40L, mediate key aspects of allergic airway inflammation in animal models of asthma, including eosinophilic airway inflammation, airway hyperresponsiveness, and T helper 2 polarization. We sought to examine OX40/OX40L and interleukin (IL)-4 expression in asthma across severities.


METHODS
Bronchial biopsies were obtained from 27 subjects with asthma (mild Global Initiative for Asthma [GINA] 1 [n = 10], moderate GINA 2-3 [n = 7], and severe GINA 4-5 [n = 10]) and 13 healthy controls. The number of OX40(+), OX40L(+), IL-4(+), and IL-4 receptor alpha (IL-4Ralpha)(+) cells in the lamina propria and airway smooth muscle (ASM) bundle and the intensity of IL-4Ralpha(+) expression by the ASM were assessed.


RESULTS
The number of OX40(+), OX40L(+), and IL-4(+) cells in the lamina propria and OX40(+) and IL-4(+) cells in the ASM bundle was significantly increased in subjects with mild asthma, but not in those with moderate or severe asthma, compared with healthy controls. In the subjects with asthma, OX40/OX40L expression was positively correlated with the number of eosinophils and IL-4(+) cells in the lamina propria. The number of IL-4Ralpha(+) cells in the lamina propria was significantly increased in moderate-to-severe disease, but not in mild asthma, compared with controls. IL-4Ralpha expression by the ASM bundle was not different among groups.


CONCLUSIONS
OX40/OX40L expression is increased in the bronchial submucosa in mild asthma, but not in moderate-to-severe disease, and is related to the degree of tissue eosinophilia and IL-4 expression. Whether these costimulatory molecules have a role as targets for asthma requires further investigation.
Siddiqui
Salman
S
Institute of Lung Health, Department of Infection, Inflammation and Immunity, University of Leicester, Leicester, LE3 9QP, England.
Mistry
Vijay
V
Doe
Camille
C
Stinson
Sally
S
Foster
Martyn
M
Brightling
Christopher
C
D000328:Adult; D001249:Asthma / Q000378:metabolism* / Q000473:pathology; D001706:Biopsy; D001980:Bronchi / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000378:metabolism / Q000473:pathology; D053278:OX40 Ligand / Q000378:metabolism*; D011657:Pulmonary Eosinophilia / Q000378:metabolism / Q000473:pathology; D019948:Receptors, Interleukin-4 / Q000378:metabolism; D053262:Receptors, OX40 / Q000378:metabolism*; D012720:Severity of Illness Index
D053278:OX40 Ligand; D019948:Receptors, Interleukin-4; D053262:Receptors, OX40; C505716:TNFRSF4 protein, human; C089251:TNFSF4 protein, human; D015847:Interleukin-4