| First Author | Perona-Wright G | Year | 2010 |
| Journal | J Immunol | Volume | 184 |
| Issue | 2 | Pages | 615-23 |
| PubMed ID | 20018622 | Mgi Jnum | J:159399 |
| Mgi Id | MGI:4442546 | Doi | 10.4049/jimmunol.0902408 |
| Citation | Perona-Wright G, et al. (2010) Differential regulation of IL-4Ralpha expression by antigen versus cytokine stimulation characterizes Th2 progression in vivo. J Immunol 184(2):615-23 |
| abstractText | 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-4Ralpha 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-4Ralpha on bystander CD4+ T cells in the draining lymph node, while simultaneously resulting in the loss of IL-4Ralpha expression on activated Th2 cells. IL-4Ralpha 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-4Ralpha upregulation and a correspondingly attenuated Th2 response. Indeed, the enhanced IL-4Ralpha upregulation in BALB/c mice, compared with that in C57BL6 mice, predicted their stronger Th2 response. The selective downregulation of IL-4Ralpha on highly activated Th cells was triggered by antigenic stimulation, was accompanied by loss of IL-7Ralpha, 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. |
