Allergy-driven alternative splicing of IL-13 receptor α2 yields distinct membrane and soluble forms

Yasuhiro Tabata, Weiguo Chen, Manoj R. Warrier, Aaron M. Gibson, Michael O. Daines, Gurjit K. Khurana Hershey

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

IL-13 is a key mediator of allergic inflammation. Its diverse functions are mediated by a complex receptor system including IL-4Rα, IL-BRα1, and IL-13Rα2. IL-4Rα and IL-13Rα1 form a high-affinity signaling heterodimer. IL-13Rα2 binds IL-13 with high affinity and has been found to exist in membrane and soluble forms. Soluble IL-13Rα2 has been postulated as a critical endogenous modulator of IL-13 responses. However, the mechanism of generation for the soluble form remains unclear. We present the initial study that a mechanism for generation of the soluble form is alternative splicing and that alternative splicing yields a distinct form of soluble IL-13Rα2. We found that several mouse organs expressed two IL-13Rα2 transcripts, the 1152-bp transcript encoding the full-length protein and the 1020-bp transcript lacking exon10, which encodes the transmembrane region. Deletion of exon 10 (ΔEx10) caused a frameshift resulting in a different amino acid sequence from position 327 to position 339 and early termination. Constructs encoding both splice variants were transfected into WEHI-274.1 cells. Transfectants expressing the full-length transcript had IL-13Rα2 on the cell surface but produced minimal soluble IL-13Rα2 in the supernatants. In contrast, transfectants expressing the ΔEx10 transcript displayed no membrane IL-13Rα2 but secreted high levels of soluble IL-13Rα2 capable of inhibiting IL-13 signaling. Both variants bound IL-13, but the ΔEx10 variant displayed ∼2-fold increase in IL-13 binding activity. Expression of the two IL-13Rα2 transcripts was differentially regulated in vivo in an experimental allergic asthma model. Thus, alternatively spliced variants of IL-13Rα2 may have a distinct biologic function in vivo.

Original languageEnglish (US)
Pages (from-to)7905-7912
Number of pages8
JournalJournal of Immunology
Volume177
Issue number11
DOIs
StatePublished - Dec 1 2006
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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