Myburgh, E. , Horsnell, W. G.C., Cutler, A. J., Arendse, B., Kubo, M. and Brombacher, F. (2008) Murine IL-4 is able to signal via chimeric human IL-4Rα/mouse γ-chain receptor. Molecular Immunology, 45(5), pp. 1327-1336. (doi: 10.1016/j.molimm.2007.09.009)
Full text not currently available from Enlighten.
Abstract
Human IL-4Rα binds to mouse γc 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-4Rα transgenic mice on a mouse IL-4Rα-deficient background (hIL-4Rα Tg/mIL-4Rα−/−). The integrity of lymphocyte-specific hIL-4Rα expression in hIL-4Rα Tg/mIL-4Rα−/− 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-4Rα Tg/mIL-4Rα−/− 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-4Rα 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-4Rα Tg/mIL-4Rα−/− mice suggesting that mIL-4 was involved. Intercrossing hIL-4Rα Tg/mIL-4Rα−/− 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-4Rα/mγc chimeric receptor in vivo.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Myburgh, Dr Elmarie |
| Authors: | Myburgh, E., Horsnell, W. G.C., Cutler, A. J., Arendse, B., Kubo, M., and Brombacher, F. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Molecular Immunology |
| Publisher: | Elsevier |
| ISSN: | 0161-5890 |
| ISSN (Online): | 1872-9142 |
University Staff: Request a correction | Enlighten Editors: Update this record
Deposit and Record Details
Deposit and Record Details