Fig. 7: E2-mediated regulation of CD2 is conserved in humans.

a Genetic association data showing association between CD2 polymorphisms and rheumatoid arthritis (RA) in female (top) and male (bottom) patients (EIRA cohort, n = 1341 males and 3361 females). b Effect of indicated SNPs on expression of CD2 in human spleen as determined from GTEx database⁶⁵. Number of samples is given in parenthesis below the graphs. Violin plots show Kernel density estimate KDE in green, interquartile ranges (25th/75th percentiles) in grey (squares), and the median in white (line). P values were obtained from GTEx, calculations are detailed in Oliva et al.⁶⁵. c CD2 expression in synovia from RA patients plotted against disease activity (DAS28-CRP). Data was extracted from GEO Dataset GSE45867. R² and P were calculated using simple liner regression. d Expression of CD2 in synovial tissue from RA patients, osteoarthritis (OA) patients or healthy controls (GEO GDS5401-3). Females are shown in red and males in blue. e Expression of CD2 in PBMCs from healthy males and females (GEO GDS5363). f CD2 expression on antigen experienced CD45RO⁺or naïve CD45RA⁺CD4⁺T cells from blood of a healthy donor. Data is representative of n = 3 independent human biological replicates. The experiment was done twice with similar results. g, h CD2 expression in CD45RO⁺T cells after 24 h incubation with 10–100 nM E2. Representative flow cytometry histogram showing CD2 expression in g and quantification in h. Data shown is pooled from two independent experiments. In all figures, each dot indicates one independent human biological replicate. Data are summarised as mean (SEM). In d, e, and g, statistical significance was evaluated using a two-tailed non-parametric Mann–Whitney U test. Sequential flow cytometry gating strategies for f–h are provided in Supplementary fig. 16.