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Page 16 of 32 Noor et al. Neuroimmunol Neuroinflammation 2019;6:10 I http://dx.doi.org/10.20517/2347-8659.2019.18

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Figure 4. Sex differences in anti-inflammatory FOXP3 and proinflammatory IL-17A from damaged sciatic nerve and in spinal cord. Tissues
were collected from behaviorally verified mice as represented in Figure 2B. (A) From ipsilateral sciatic nerve (SCN), CCI induced a significant
increase in FOXP3 mRNA expression (F 1,1 = 76.18, P < 0.0001), with CCI-treated females responding to BIRT377 treatment to a greater
degree than males (F 1,1 = 5.38, P = 0.025). (B) In the ipsilateral DRGs, FOXP3 mRNA levels were elevated following CCI (F 1,1 = 6.55, P = 0.014),
post hoc comparisons revealed significant increases in FOXP3 mRNA levels in females with CCI compared to the sham controls. (C) In the
ipsilateral lumbar spinal cord (LSC) dorsal horn, post-CCI induction in FOXP3 mRNA levels was observed in males (P = 0.0006). Following
CCI, males displayed significantly greater FOXP3 mRNA levels than in females (P = 0.001). BIRT377 treatment reduced FOXP3 in males with
CCI (P < 0.0001), a significant interaction between surgery, injection, and sex (F 1,1 = 6.5, P = 0.014) was observed. (D) In the contralateral
dorsal horn, FOXP3 levels were comparable between groups. (E) Post-CCI IL-17A mRNA levels were significantly elevated at the ipsilateral
sciatic nerve (F 1,1 = 21.93, P < 0.0001). BIRT377 treatment reduced post-CCI IL-17A mRNA levels (F 1,1 = 21.93, P < 0.0001), with post hoc
comparisons revealing a significant reduction of IL-17A mRNA levels following BIRT377 treatment in females with CCI. (F) In the ipsilateral
dorsal horn, post-CCI IL-17A mRNA levels were elevated (F 1,1 = 14.85, P = 0.0004). BIRT377 treatment reduced IL-17A mRNA levels in mice
with CCI (F 1,1 = 14.07, P = 0.0006), which occurred in females to much a greater degree than males (F 1,1 = 5.71, P = 0.02). Post-CCI induction
in IL-17A mRNA levels were much greater in females, than in males (F 1,1 = 5.23, P = 0.02). *p values from post hoc comparisons ranges from
P = 0.04 to P < 0.0001. n = 5 in female CCI + BIRT data for DRG FOXP3. n = 6 per group unless otherwise indicated