Fig. 6: Inflammatory cytokines modulate Foxo1 expression in T cells.
a p value/Z score dot-plots representing all Upstream Regulators (left panel), the cytokines and cytokines-related regulators (middle panel) and among these ones, those with a Z score >2 (right panel) determined by Ingenuity Pathway Analysis software as significantly (p < 0.05) involved in the transcriptomic signature of CD4N cells from old WT mice. b Representation of the 4 most significant GSEA Hallmarks gene sets retrieved in the transcriptomic signature of CD4N cells from old WT mice. c Purified T cells from young WT mice were cultured for 4 days with IL-7 alone or together with the indicated cytokines. Diagram illustrating the experimental model. d Relative Foxo1 MFIs for CD4N, CD4M and CD4R cells recovered after 4 days of culture with IL-7 alone or together with the indicated cytokines. Relative MFIs were calculated after barcoding by dividing the MFI of a given T-cell subset in the presence of one given cytokine by the MFI of the same T-cell subset cultured with IL-7 alone. e Diagram illustrating the experimental model depicted in GSE75202 and GSE124829 from the Immunological Genome Project Consortium. f A list of genes up- or down-regulated in CD4 T cells by type 1 interferons was determined from GSE75202 (Supplementary Data 5). Expression of these genes by CD4N cells from old WT mice was visualized using the GSEA software. g Relative Foxo1 and Foxo3 expressions from GSE75202 and GSE124829 were determined by dividing for each mouse the corresponding counts by the average number of counts in the control group. h GSEA analysis visualizing the expression of genes down- or up-regulated in Foxo1-deficient CD4N cells (Supplementary Data 1) by CD4 T cells from the spleen of mice treated as illustrated in (e). i A list of genes for which Foxo1 binds in the promoter region was determined from GSE46525 (Supplementary Data 6). GSEA analysis visualizing the expression of these genes by CD4 T cells from the spleen of mice treated as illustrated in (e). Quantifications are represented as Means ± SEM. The significance of differences between two series of results was assessed using Student’s unpaired t test (a, d, g). The p-values for the GSEA test statistics are calculated by permutation (b, f, h, i). Significant (p < 0.05) p-values are indicated. Source data are provided as a Source Data file.
