Cutting Edge: Polymorphisms in the ICOS Promoter Region Are Associated with Allergic Sensitization and Th2 Cytokine Production
Year: 2005
Type: article
Study design: Observational Study
Abstract: The establishment of ICOS as an important regulator of Th2 development and effector function makes the ICOS locus an attractive candidate for Th2-mediated diseases, such as asthma and allergy. In evaluation of this candidate locus in humans, we identified 11 variants and determined that two in the putative promoter region are significantly associated with allergic sensitization and serum IgE levels. In addition, cultures of activated PBMCs from individuals homozygous for the associated polymorphisms produced increased levels of the Th2 cytokines, IL-4, IL-5, and IL-13, as well as TNF-alpha compared with controls. One of the polymorphisms, -1413G/A, demonstrated differential NF-kappaB binding in mobility shift analysis, suggesting that this polymorphism has functional consequences. Overall, these data demonstrate that ICOS is a susceptibility gene for allergic sensitization, perhaps through the promotion of Th2 differentiation.
Source: The Journal of Immunology
Institution: University of Chicago
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: SCOR in Cellular and Molecular Mechanisms of Asthma, The role of ICOS in allergic airway disease, Immunologic Aspects of Disease, Molecular Mechanisms of Asthma, G3887688075, G4973474899, CHARACTERIZING A 5P-LINKED BHR SUSCEPTIBILITY LOCUS, G8025765072, G830274963, G875187158, OTOLARYNGOLOGY-HEAD AND NECK SURGERY TRAINING PROGRAM, G895356327
OpenAlex ID: W1790729235