Phenotypic and genotypic association of epithelialIL1RL1to human TH2-like asthma

    loading  Checking for direct PDF access through Ovid

Abstract

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 forIL1RL1in 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 inIL1RL1, possibly explaining its genetic relationship with asthma. We also sought to evaluate the regulation of ST2L and sST2in 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 inIL1RL1were 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 inIL1RL1were 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 expressionin vitroin primary human epithelial cells.

Conclusion:

Both pathologic and genetic approaches support a role forIL1RL1in severe asthma, as well as TH2-lke asthma, suggesting that targeting this pathway may have therapeutic benefits.

Related Topics

    loading  Loading Related Articles