Perona-Wright, G. , Mohrs, K., Mayer, K. D. and Mohrs, M. (2010) Differential regulation of IL-4R expression by antigen versus cytokine stimulation characterizes Th2 progression in vivo. Journal of Immunology, 184(2), pp. 615-623. (doi: 10.4049/jimmunol.0902408) (PMID:20018622) (PMCID:PMC3066071)
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Abstract
IL-4 promotes Th2 differentiation and provides immunity to helminth infections but is also associated with allergy and asthma. This suggests that precise adjustment of IL-4 responsiveness is needed to correctly balance immune responses. The IL-4Rα chain is an essential component of the IL-4 receptor and signals via STAT6. In this study, we show that infection with a helminth pathogen elicited broad upregulation of IL-4Rα on bystander CD4+ T cells in the draining lymph node, while simultaneously resulting in the loss of IL-4Rα expression on activated Th2 cells. IL-4Rα upregulation was restricted to the reactive lymph node, occurred within 4 d of infection, and was driven by an IL-4– and STAT6–dependent mechanism. Mice heterozygous for Stat6 exhibited reduced IL-4Rα upregulation and a correspondingly attenuated Th2 response. Indeed, the enhanced IL-4Rα upregulation in BALB/c mice, compared with that in C57BL6 mice, predicted their stronger Th2 response. The selective downregulation of IL-4Rα on highly activated Th cells was triggered by antigenic stimulation, was accompanied by loss of IL-7Rα, and rendered the cells unresponsive to IL-4. Together these data reveal a tightly controlled program of changing IL-4 responsiveness that characterizes the initiation, amplification, and restriction of a Th2 response in vivo.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Perona-Wright, Dr Georgia |
| Authors: | Perona-Wright, G., Mohrs, K., Mayer, K. D., and Mohrs, M. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Journal of Immunology |
| Publisher: | American Association of Immunologists |
| ISSN: | 0022-1767 |
| ISSN (Online): | 1550-6606 |
| Published Online: | 06 January 2010 |
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