Phenotypic and genotypic association of epithelial IL1RL1 to human TH2-like asthma

Russell S. Traister, Crystal E. Uvalle, Gregory A. Hawkins, Deborah A. Meyers, Eugene R. Bleecker, Sally E. Wenzel

Research output: Contribution to journalArticlepeer-review

46 Scopus citations


Background Severe asthma remains poorly characterized, although it likely consists of at least 1 phenotype with features of TH2-like inflammation. IL1RL1, encoding both the IL-33 receptor, ST2L, and decoy receptor, sST2, has been genetically associated with asthma, though the mechanism for susceptibility remains unknown.

Objective Given previous data supporting a role for IL1RL1 in TH2 inflammation, we hypothesized that ST2L expression might be increased in TH2-like asthma and that expression levels would be associated with single nucleotide polymorphisms in IL1RL1, possibly explaining its genetic relationship with asthma. We also sought to evaluate the regulation of ST2L and sST2 in vitro.

Methods Endobronchial brushings and biopsies were obtained and expression of ST2L compared by severity levels, as well as by TH2-like biomarkers. Subjects were genotyped and the relationship of dichotomous expression of ST2L and sST2 to single nucleotide polymorphisms in IL1RL1 were determined. Epithelial cells were grown in air-liquid interface culture, and ST2L and sST2 responses to IFN-γ and IL-13 were evaluated.

Results ST2L expression was increased in severe asthma (P =.02) and associated with multiple indicators of TH2-like inflammation, including blood eosinophils (P =.001), exhaled nitric oxide (P =.003), and epithelial CLCA1 (P <.0001) and eotaxin-3 (P =.001) mRNA expression. Multiple single nucleotide polymorphisms in IL1RL1 were found in relation to dichotomous expression of both ST2L and sST2. sST2 expression was associated with IFN-γ expression in bronchoalveolar lavage, while inducing its expression in vitro in primary human epithelial cells.

Conclusion Both pathologic and genetic approaches support a role for IL1RL1 in severe asthma, as well as TH2-lke asthma, suggesting that targeting this pathway may have therapeutic benefits.

Original languageEnglish (US)
Pages (from-to)92-99.e10
JournalJournal of Allergy and Clinical Immunology
Issue number1
StatePublished - Jan 1 2015
Externally publishedYes


  • Asthma
  • IL1RL1
  • ST2L
  • T2 inflammation
  • sST2
  • single nucleotide polymorphisms

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


Dive into the research topics of 'Phenotypic and genotypic association of epithelial IL1RL1 to human TH2-like asthma'. Together they form a unique fingerprint.

Cite this