Cutting edge: Polymorphisms in the ICOS promoter region are associated with allergic sensitization and Th2 cytokine production

Rebecca A. Shilling, Jayant M. Pinto, Donna C. Decker, Daniel H. Schneider, Hozefa S. Bandukwala, Jeffrey R. Schneider, Blanca Camoretti-Mercado, Carole Ober, Anne I. Sperling*

*Corresponding author for this work

Research output: Contribution to journalArticle

40 Scopus citations

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-α compared with controls. One of the polymorphisms, -1413G/A, demonstrated differential NF-κB 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.

Original languageEnglish (US)
Pages (from-to)2061-2065
Number of pages5
JournalJournal of Immunology
Volume175
Issue number4
DOIs
StatePublished - Aug 15 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Shilling, R. A., Pinto, J. M., Decker, D. C., Schneider, D. H., Bandukwala, H. S., Schneider, J. R., Camoretti-Mercado, B., Ober, C., & Sperling, A. I. (2005). Cutting edge: Polymorphisms in the ICOS promoter region are associated with allergic sensitization and Th2 cytokine production. Journal of Immunology, 175(4), 2061-2065. https://doi.org/10.4049/jimmunol.175.4.2061