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

39 Citations (Scopus)

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
StatePublished - Dec 1 2006
Externally publishedYes

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Interleukin-13 Receptors
Interleukin-13
Alternative Splicing
Hypersensitivity
Membranes
Exons
Inflammation Mediators
Amino Acid Sequence
Asthma

ASJC Scopus subject areas

  • Immunology

Cite this

Tabata, Y., Chen, W., Warrier, M. R., Gibson, A. M., Daines, M. O., & Khurana Hershey, G. K. (2006). Allergy-driven alternative splicing of IL-13 receptor α2 yields distinct membrane and soluble forms. Journal of Immunology, 177(11), 7905-7912.

Allergy-driven alternative splicing of IL-13 receptor α2 yields distinct membrane and soluble forms. / Tabata, Yasuhiro; Chen, Weiguo; Warrier, Manoj R.; Gibson, Aaron M.; Daines, Michael O; Khurana Hershey, Gurjit K.

In: Journal of Immunology, Vol. 177, No. 11, 01.12.2006, p. 7905-7912.

Research output: Contribution to journalArticle

Tabata, Y, Chen, W, Warrier, MR, Gibson, AM, Daines, MO & Khurana Hershey, GK 2006, 'Allergy-driven alternative splicing of IL-13 receptor α2 yields distinct membrane and soluble forms', Journal of Immunology, vol. 177, no. 11, pp. 7905-7912.
Tabata Y, Chen W, Warrier MR, Gibson AM, Daines MO, Khurana Hershey GK. Allergy-driven alternative splicing of IL-13 receptor α2 yields distinct membrane and soluble forms. Journal of Immunology. 2006 Dec 1;177(11):7905-7912.
Tabata, Yasuhiro ; Chen, Weiguo ; Warrier, Manoj R. ; Gibson, Aaron M. ; Daines, Michael O ; Khurana Hershey, Gurjit K. / Allergy-driven alternative splicing of IL-13 receptor α2 yields distinct membrane and soluble forms. In: Journal of Immunology. 2006 ; Vol. 177, No. 11. pp. 7905-7912.
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