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Challenging Evolution: Eliminating the IFN-gamma 3 ARE Effects T Cell Homeostasis
Deborah L , H.; Cyril, B.; Jeff, S.; Veronique, P.; William, B.; Xin, C.; Matthew, B.; Thomas, W.; Howard A, Y.
2007-07-01
Source PublicationCytokine
AbstractInterferon (IFN) gamma is a pleiotropic cytokine that impacts a variety of immune functions. The importance of this cytokine requires tight control of its expression. This regulation is complex and involves both transcriptional and post-transcriptional mechanisms. The 30 untranslated region (30 UTR) of the IFN-gamma mRNA contains a highly conserved 100 nucleotide sequence. Embedded in this sequence are multiple AU-rich elements (AREs) which function in mRNA stabilization and translational silencing. To study the impact of these sequences on IFN-gamma expression, we have created an IFN-gamma ARE knock-out mouse. Elimination of the ARE does not impair transcription nor does it inhibit functional IFN-gamma protein synthesis. Mice lacking the IFN-gamma-specific ARE have chronic low levels of IFN-gamma in their serum. Additionally,upon IL-12 stimulation, these mice produce 3- to 5-fold more IFN-gamma than their wild type littermate controls. The mice have increased cellularity in both spleen and liver which is due to increased numbers of NKT, CD4+ and CD8+ T cells in both organs. In thymi, the percentage of CD4+ and CD8+ T cells are increased and these cells express lower levels of CD24 and CD69 suggesting a more mature T cell phenotype. Furthermore the Tregs in the KO mice are more suppressive than the Tregs from WT littermates. Currently, studies are underway to investigate the impact of altered IFN-gamma expression on multiple levels of immunological development and function.
KeywordIFN-gamma 3 ARE T Cell Homeostasis
URLView the original
Language英語English
The Source to ArticlePB_Publication
PUB ID47027
Document TypeConference paper
CollectionInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Deborah L , H.,Cyril, B.,Jeff, S.,et al. Challenging Evolution: Eliminating the IFN-gamma 3 ARE Effects T Cell Homeostasis[C], 2007.
APA Deborah L , H.., Cyril, B.., Jeff, S.., Veronique, P.., William, B.., Xin, C.., Matthew, B.., Thomas, W.., & Howard A, Y. (2007). Challenging Evolution: Eliminating the IFN-gamma 3 ARE Effects T Cell Homeostasis. Cytokine.
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