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. 2016 Sep 1;113(38):10637–10642. doi: 10.1073/pnas.1607101113

Fig. 4.

Fig. 4.

Leptin promotes spontaneous SLE in NZB/W mice, and leptin blockade by anti-leptin Ab delays SLE progression and prolongs survival of NZB/W lupus mice. (A) Increased plasma leptin in aging female untreated lupus-prone NZB/W mice (n = 16) followed longitudinally from 6 to 34 wk of age. (B) Accelerated development of proteinuria (>100 mg/dL) in NZB/W mice after treatment with leptin (open circles, n = 14) vs. saline-treated controls (n = 16, open squares) using the protocol described in Materials and Methods. (C) ELISA for anti-dsDNA autoAb at 12 wk of age in mice treated as in B, with leptin (closed circles) or saline (open circles). (D) AutoAb in NZB/W mice treated as in B, with leptin (closed circles) and saline-treated controls (open circles) at different ages. The dashed line indicates the threshold of positivity. *P < 0.0001; §P < 0.003; †P < 0.01; ‡P < 0.05. (E) Severely nephritic NZB/W mice (proteinuria ≥300 mg/dL) were randomly divided into two groups (n = 11 each) and given either a single i.p. injection of 150 μg anti-leptin Ab (closed circles) or isotype-matched control Ab (open circles). Survival was monitored for the following 9 wk. P < 0.007. (F–H) Tregs expansion that occurs after leptin inhibition in vivo (30) associates with suppression of anti-dsDNA autoAb in diseased NZB/W lupus mice. Ex vivo-labeled (CFSE) Tregs were adoptively transferred into old NZB/W mice that had received a single i.p. injection of 150 μg anti-leptin Ab/mouse at 24 and 12 h before Tregs transfer. Arrows indicate the direction of transfer of mouse donor cells into host. Untreated young mice (y) were included as controls. Comparisons were made between old diseased NZB/W lupus mice receiving Tregs from young premorbid mice following leptin-blockade or mock treatment. Data are shown before (0) and at day 3 and 10 after Tregs transfer. Plasma leptin concentration (measured by ELISA) (F) and anti-DNA autoAb (G) before and after transfer of Tregs and expansion of Tregs (CFSE-gated) in vivo after leptin blockade (H). Mean ± SEM of cumulative data from two independent experiments (n = 8 per group). *P < 0.05; **P < 0.01; ***P < 0.005.