Fig. 5: Altered Treg signatures in children with T1D and validation in independent datasets. | Nature Communications

Fig. 5: Altered Treg signatures in children with T1D and validation in independent datasets.

From: Imbalance of stem-like and effector T cell states in children with early type 1 diabetes across conventional and regulatory subsets

Fig. 5

A Gene set enrichment analysis (GSEA) of genes up- or downregulated in IPEX patients vs. healthy donors (refs. 65,66) tested against ranked DEGs in Tregs from children with T1D vs. healthy donors. P-values estimated using adaptive multi-level split Monte Carlo (fgsea R package). B Correlation between fasting C-peptide at T1 and IL4R (left) or IL10RA (right) expression within Tregs at T0. P-values from two-sided Pearson correlation; n = 28 T1D donors. Line = regression fit; shaded area = 95% CI. C Correlation between fasting C-peptide at T1 and frequency of Treg1 (left) or Treg4 (right) at T0. P-values, line, and shaded area as in (B); n = 28 T1D donors. D–G Reanalysis of Treg populations in published datasets: GSE221297 (PBMC, 5 T1D, 3 healthy), ParseBio (PBMC, 12 T1D, 12 healthy), and HPAP (splenocytes, 4 T1D, 8 non-diabetic). D UMAP projection of Treg cells, colored by Louvain clusters. E Density plots showing distribution differences of Tregs from healthy vs. T1D donors. F Heatmaps of selected marker genes per cluster (row-scaled z-scores of average expression). G Quantification of cluster frequencies per sample. Boxplots: line = median, hinges = first and third quartiles, whiskers = 1.5 × IQR. H Average frequency of Treg subclusters in healthy (blue) and T1D (red) donors across datasets. Clusters Treg1–4 in our study matched to TregA–D here. P-values by paired t test. HD – Healthy Donor, IPEX - Immunodysregulation polyendocrinopathy enteropathy X-linked syndrome, T1D – Type 1 Diabetes Mellitus, T1 – timepoint one year after diagnosis.

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