| Gene name: | FOXO1 |
| Aging type: | Prevent |
| Aging characteristic: |
| Tissue type: | -- |
| Cell name: | CD8+T |
| Experiment: | Cytokine assay//Flow cytometry |
| Description: | In Foxo1-KO T cells, CD28 was uniformly reduced in naive T cells, and it was even more reduced in P14 Foxo1-KO KLRG1low day 30 post-infection T cells, compared with WT. A further indication of senescence is the inability of T cells to produce effector cytokines upon stimulation: TNF, IFN-γ, and interleukin-2 (IL-2). This was measured as the proportion of cytokine-expressing T cells (positive for TNF, IFN-γ, or both), and was found to be diminished in T cells from Foxo1-KO mice compared with WT. Furthermore, the ability to simultaneously produce multiple cytokines, especially TNF, IFN-γ, and IL-2, is a property of functional memory T cells, and as depicted in Figure 5G, Foxo1-KO mice possessed proportionately fewer double- and triple-cytokine-producing T cells. |
| Target gene: | BACH2//AP-1 |
| Official symbol(s): | BACH2//AP-1 |
| R-AG-Target gene: | Upregulation//Downregulation |
| Subcategory: | Unclear |
| Target gene experiment: | CHIP-Seq//ATAC-seq//qRT-PCR |
| Target gene description: | We found that FOXO1 exhibited genomic binding within and proximal to the Bach2 gene locus at multiple sites in naive and day 12 p.i. cells. We observed that Bach2 becomes FOXO1 dependent only post-activation. Whereas naive WT and Foxo1-KO cells had similar, abundant Bach2 mRNA expression, 7 and 12 days post-activation WT cells exhibited a ~4-fold increase versus Foxo1-KO cells, in both KLRG1low and KLRG1high subsets. The T cells were pre-sorted for KLRG1high and KLRG1low cells to segregate effector and memory-precursor populations. In both naive and post-infection (p.i.) T cells, among the prominent FOXO1-bound genomic sites were regulatory sequences of multiple AP-1 family members, including Fos, JunB, FosB, and JunD. FOXO1 bound to open chromatin proximal to the transcription start site (TSS) of each of these genes, or to nearby presumed enhancers (e.g., upstream of Fos). Found for both naive and day 12 P14 T cells, these data are consistent with FOXO1 acting as a direct or indirect co-repressor for genes that mediate T cell activation and differentiation. |
| Regulatory pathway: | -- |
| R-AG-Pathway: | -- |
| Pathway experiment: | -- |
| Pathway description: | -- |
Annotation:
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