Figure 2. Expanding mTreg alleviates nociception dependent on sex hormones and independent of tissue repair.

(A) Schematic representation of the spared nerve injury (SNI) surgery. (B) Long-term assessment of mechanical thresholds in mice following SNI surgery (both sexes combined, no difference between the sexes). n = 7–8 mice per group. (C and D) Percent response to 0.008 g von Frey filament in mice with SNI (day 0) and treated with IT pegDT or vehicle every 4 days. n = 8 per group for females and 9–10 per group for males. (E) Schematic representation of mTreg expansion in mice 4 weeks after SNI by 3 IT injections of low-dose IL-2 (0.1 μg). (F) Total mTreg number in meninges after low-dose IL-2 or vehicle IT injections (both sexes combined, no differences between the sexes). (G and H) Nociceptive thresholds of females (G) and male (H) mice given low-dose IL-2 or vehicle IT 4 weeks after SNI. (I) Schematic representation of the mating strategy of Four Core Genotypes (FCG) FoxP3-DTR mice demonstrating resulting XX and XY females and XX and XY male mice. (J and K) Nociceptive thresholds of FCG female (J) and male (K) mice following low-dose IL-2 or vehicle IT injections 4 weeks after SNI. (L) Anti-nociceptive efficacy determined as post IL-2/vehicle injection threshold divided by baseline mechanical threshold in male and female mice with XX (white) or XY (pink) chromosomes. (M) Nociceptive thresholds of FCG FoxP3-DTR female and male mice following a single IT pegDT or vehicle injection. (N) Percent baseline nociceptive thresholds determined as post pegDT/vehicle injection threshold divided by baseline mechanical threshold in male and female mice with XX (white) or XY (pink) chromosomes. ns = not significant, *p<0.05, **p<0.01,***p<0.001. Related to Figure S4.