Extended Data Fig. 1: Reduced CRELD1 expression in healthy individuals correlates with reduced T cell numbers and increased immunosenescence-associated signature in blood.

a, Expression of selected genes across 712 human samples of the FANTOM5 dataset ordered by anatomic region. b, Expression fold changes (FCs) in the top 100 human datasets (based on subgroup effect) listed on NCBI GEO profiles independently ranked by FC for each of the analyzed genes. Within the analyzed datasets, 1371 comparisons are interrogated. c, Distribution of expression of selected human and murine genes across the FANTOM5 specimens. d, Expression FCs in the top 100 murine datasets (based on subgroup effect) listed on NCBI GEO profiles independently ranked by FC for each of the analyzed genes. Within the analyzed datasets, 1380 comparisons are interrogated. e, Detailed schematic of the analysis performed on the 500FG dataset. f–l, Box plots of cellular counts in CRELD1^hi and CRELD1^lo groups in (f) CD4⁺ T cells (p = 0.0093), g, CD4⁺ effector memory (CCR7^–/CD45RO⁺ EM, p = 0.024) T cells, h, CD8⁺ T cells, (i) CD8⁺ EM T cells (p = 0.014, j, IgM⁺ B cells (p = 0.047), k, IgD⁺IgM⁺ B cells (p = 0.039), and (l) IgD⁺IgM⁺CD27^– B cells (p = 0.04) (n = 10, unpaired two-sided t-test, *p < 0,05 **p < 0.01 ***p < 0,001). m, Age of the donors in the CRELD1^hi and CRELD1^lo groups (n = 10). n, Correlation between IMM-AGE down and IMM-AGE up signatures with dots representing all donors in the study, colored by CRELD1 expression (p-value shown for Pearson’s correlation test of CRELD1 expression and signature enrichment, error bar shows 95^th confidence interval). o, Ratio between the number of CD4⁺ and CD8⁺ T cells for the CRELD1^hi and CRELD1^lo groups (n = 10, unpaired two-sided t-test, *p = 0.036). p, Percentage of CMV-positive donors in the CRELD1^hi and CRELD1^lo groups. q–r, Box plots of cellular counts in CMV^– CRELD1^hi and CRELD1^lo groups in (q) CD4⁺ T cells, (r) CD8⁺ T cells (n = 10, unpaired two-sided t-test, **p = 0.0043). (Box plots in figure represent median value as well as 25^th-75^th percentiles; whiskers show the 5^th-95^th percentiles.).