Fig. 6: Androgen regulation of Ptpn22 expression in T cells and the sexual dimorphism in mouse SLE model due to removal of Ptpn22.

a RT-PCR quantification of Ptpn22 transcript levels in DN (left) and CD8SP (right) thymocytes from 8-week-old B6J males that were subjected to sham-operation or castration as 4-week-olds. Mean ± sem. Significance was calculated using an unpaired t-test. n – number of mice. Sham n = 11, Castrated n = 14 (left) and n = 13 (right). Combined data from two experiments. b RT-PCR quantification of human PTPN22 transcript levels in Jurkat T cells transduced with either an empty vector (left) or an AR encoding plasmid (right) and treated with R1881 (5 nM) or carrier (0.1% EtOH) for 16 h. Mean ± sem. Significance was calculated using an unpaired t-test. Combined data from 2 experiments. n = 6/group. c Pathophysiological parameters of SLE measured in 8-10-month-old B6.NZM wild-type (filled circles) and B6.NZM.Ptpn22KO (open circles) male (blue) and female (red) mice: anti-nuclear antibodies (ANA) scores measured by immunofluorescence of HEp-2 cells with sera diluted 1:100, spleen weights, glomerulonephritis (GN) scores, and complement C3 deposits measured in kidneys using immunofluorescence. P values- one-way ANOVA with Tukey’s multiple-comparison test between males and females reflecting sex bias are shown horizontally, and values estimating differences between wild-type and KO mice are shown vertically. Number of mice: ANA - WT male n = 24, WT female n = 20, Ptpn22KO male n = 21, Ptpn22KO female n = 16; splenomegaly - WT male n = 44, WT female n = 47, Ptpn22KO male n = 26, Ptpn22KO female n = 23; GN - n = 10/group; C3 deposits - WT male n = 49, WT female n = 47, Ptpn22KO male n = 56, Ptpn22KO female n = 29. Mean ± sem. The significance of the interaction between sex and Ptpn22 mutation was calculated using 2-Way ANOVA and the difference in mean values was tested by non-parametric 1-Way ANOVA. Symbols – individual mice.