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- W4313373310 endingPage "155.13" @default.
- W4313373310 startingPage "155.13" @default.
- W4313373310 abstract "Abstract The E3 ubiquitin ligase Cullin 3 (Cul3) has been shown to play a key role in several processes in mammalian cells, including antioxidation, cell cycle regulation, and immunity. Published work has shown that T cell-specific deletion of Cul3 leads not only to a severe defect in natural killer T (NKT) cell development but also to enhanced T regulatory cell and T follicular helper cell differentiation. However, the role of Cul3 in controlling NKT and CD4 T cell proliferation, activation, and homeostasis remains unknown. To begin investigating this, we generated a tamoxifen-inducible CD4 ERT-Cre system to delete Cul3 in mature NKT cells. Surprisingly, Cul3 does not seem to play a role in NKT cell maintenance in either the spleen or the liver, yet activated NKT cells lacking Cul3 proliferate better than wild type cells. We also used a CD4-Cre driven Cul3 knockout mouse model to study CD4 T cell responses. In contrast to our NKT cell studies, the loss of Cul3 in this model severely impacted naïve and effector CD4 T cell frequencies the peripheral tissues. Interestingly, similar to NKT cells, deletion of Cul3 caused naïve CD4 T cells to proliferate better than wild type cells after activation. The proliferative advantage observed in Cul3-deficient naïve CD4 T cells appears to be IL-2 dependent, as these cells display increased IL-2 secretion and IL2Rα surface expression. Preliminary data suggests that major metabolic pathways within the cell may be differentially regulated in NKT and CD4 T cells, and we are currently investigating this possibility further. In all, Cul3 may have unique functions during NKT and CD4 T cell-mediated immune responses, and future work will focus on determining the mechanisms by which Cul3 exerts its effects on these T cell subsets." @default.
- W4313373310 created "2023-01-06" @default.
- W4313373310 creator A5028947679 @default.
- W4313373310 creator A5079580291 @default.
- W4313373310 date "2020-05-01" @default.
- W4313373310 modified "2023-09-27" @default.
- W4313373310 title "Novel roles for Cullin 3 in T cell-mediated immune responses" @default.
- W4313373310 doi "https://doi.org/10.4049/jimmunol.204.supp.155.13" @default.
- W4313373310 hasPublicationYear "2020" @default.
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