| Status | 已發表Published |
| 293 IFN-γ 3′untranslated region AU-RICH element-deleted mice have altered immune structure and function | |
Deborah, L.; Cyril, B.; Jeff, S.; William, B.; Xin, C. ; Vincenzo, C.; Matthew, B.; Thomas, W.; Isabelle, S.; Howard A., Y.
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| 2008-09-01 | |
| Source Publication | CYTOKINE
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| Abstract | Interferon (IFN)-γ is a critical regulator of immune function whose expression is tightly regulated at both the transcriptional and post-transcriptional levels. Our current studies focus on a highly conserved 162 nucleotide sequence in the 3′untranslated region (UTR) of the IFN-γ mRNA. This putative control element contains multiple AU-rich elements (AREs) that function in mRNA stabilization and translational silencing. To study the impact of this sequence on IFN-γ gene expression and immune function, we created an IFN-γ 3′UTR ARE-deleted mouse. ARE elimination results in chronic low levels of circulating IFN-γ. These levels are independent of cellular stimulation and are not present in littermate control mice. IFN-γ effects are widespread in the 3′UTR ARE-deleted mice and result in increased cellularity and altered secondary immune organ structure. In liver, perivascular cuffing by both lymphoid and myeloid cells occurs, a phenomenon observed in inflammatory states and chronic infections. Lymph nodes and spleen are slightly enlarged and the architecture of these organs as well as the thymus is highly remodeled. In particular, the cortex and paracortex regions of lymph nodes are less defined. Cortical B-cell rich follicular areas found in normal lymph nodes are distorted and absent. The thymi of these mice have distorted follicles as well as a dramatic influx of B cells. To examine immune function, the 3′UTR ARE-deleted mice were injected with IL-12 resulting in 3- to 5-fold more IFN-γ production than their wild type littermates. To assess whether regulatory immune function was altered, we measured T-regulatory (T-reg) cell activity and found that T-reg cells from 3′UTR ARE-deleted mice were better inhibitors of effector T cell proliferation than T-regs from WT littermate controls. Collectively, these data suggest that targeted deletion of the 3′UTR ARE affects not only IFN-γ expression but has profound effects on immune organization and function. |
| Keyword | IFN-γ 3′ AU-RICH element immune structure and function |
| URL | View the original |
| Language | 英語English |
| The Source to Article | PB_Publication |
| PUB ID | 46992 |
| Document Type | Conference paper |
| Collection | Institute of Chinese Medical Sciences |
| Recommended Citation GB/T 7714 | Deborah, L.,Cyril, B.,Jeff, S.,et al. 293 IFN-γ 3′untranslated region AU-RICH element-deleted mice have altered immune structure and function[C], 2008. |
| APA | Deborah, L.., Cyril, B.., Jeff, S.., William, B.., Xin, C.., Vincenzo, C.., Matthew, B.., Thomas, W.., Isabelle, S.., & Howard A., Y. (2008). 293 IFN-γ 3′untranslated region AU-RICH element-deleted mice have altered immune structure and function. CYTOKINE. |
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