Murine IL-4 is able to signal via chimeric human IL-4Ralpha/mouse gamma-chain receptor

Elmarie Myburgh, William G C Horsnell, Antony J Cutler, Berenice Arendse, Masato Kubo, Frank Brombacher

Research output: Contribution to journalArticlepeer-review


Human IL-4Ralpha binds to mouse gammac resulting in a chimeric receptor specific for human IL-4 but not mouse IL-4, providing in principle an inducible hIL-4 system. We investigated the in vitro and in vivo characteristics of human IL-4Ralpha transgenic mice on a mouse IL-4Ralpha-deficient background (hIL-4Ralpha Tg/mIL-4Ralpha(-/-)). The integrity of lymphocyte-specific hIL-4Ralpha expression in hIL-4Ralpha Tg/mIL-4Ralpha(-/-) mice was demonstrated by FACS analysis. This was confirmed in functional studies as lymphocytes responded to recombinant hIL-4 but not mIL-4 or mIL-13 in proliferation and T helper differentiation assays, demonstrating species-specificity and inducibility of the chimeric receptor in vitro. We then infected transgenic mice with Nippostrongylus brasiliensis, known to induce a strong Type 2 response in wild-type mice. As expected hIL-4Ralpha Tg/mIL-4Ralpha(-/-) mice were unable to expel N. brasiliensis worms which confirms unresponsiveness in non-lymphocytes. However they developed a Th2 cytokine and IgE response in the absence of induction with hIL-4. These results suggested that lymphocyte-specific IL-4Ralpha responsiveness was still present in vivo. Neutralization of endogenous mIL-4 resulted in inhibition of N. brasiliensis-induced Th2 cytokine and total IgE production in hIL-4Ralpha Tg/mIL-4Ralpha(-/-) mice suggesting that mIL-4 was involved. Intercrossing hIL-4Ralpha Tg/mIL-4Ralpha(-/-) mice with mIL-4(-/-)/mIL-13(-/-) mice completely abrogated Type 2 responses in N. brasiliensis infections. Together, these data demonstrate that mIL-4 triggered the hIL-4Ralpha/mgammac chimeric receptor in vivo.

Original languageEnglish
Pages (from-to)1327-36
Number of pages10
JournalMolecular immunology
Issue number5
Publication statusPublished - Mar 2008


  • Animals
  • CD4-Positive T-Lymphocytes/immunology
  • Humans
  • Interleukin Receptor Common gamma Subunit/immunology
  • Interleukin-4/metabolism
  • Interleukin-4 Receptor alpha Subunit/genetics
  • Mice
  • Mice, Transgenic
  • Nippostrongylus/immunology
  • Recombinant Fusion Proteins
  • Signal Transduction/immunology

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