USP25 attenuates anti-GBM nephritis in mice by negative feedback regulation of Th17 cell differentiation

Figures & data

Figure 1. Knockout USP25 aggravated the renal injury in anti-GBM GN: (A) Representative photographs of the deposition of sheep IgG and mouse IgG in the kidneys of WT anti-GBM GN mice and USP25^−/− anti-GBM GN mice; (B) pathological changes in renal tissues in wild anti-GBM GN mice and USP25^−/− anti-GBM GN mice; (C and D) quantification deposition of sheep IgG and mouse IgG; (E and F) Scr (E) and BUN (F) of USP25^−/− anti-GBM GN mice and wild anti-GBM GN mice; (G) the proportion of crescent formation at the day 21. Anti-GBM GN: anti-glomerular basement membrane glomerulonephritis; Scr: serum creatinine; BUN: blood urea nitrogen; WT: wild type; bars represent means ± SEM; n = 5/group; ^#p < 0.05; ^##p < 0.01.

Figure 2. Knockout of USP25 increased Th17 cells in vivo: (A and B), proportion of spleen Th1, Th2, Th17 in wild mice and USP25^−/− mice 14 days after establishment of the anti-GBM GN; Anti-GBM GN: anti-glomerular basement membrane glomerulonephritis; WT: wild type; bars represent means ± SEM; n = 3–5 each group; ^#p < 0.05; ^##p < 0.01.

Figure 3. Percentage of positive cells after CD4+ T cell induced in vitro of USP25^−/− mice and WT mice. WT: wild type; bars represent means ± SEM; n = 3–5 each group; ns: none significance; ^##p < 0.01.

Figure 4. Knockout of USP25 increase transcription of RORγt in vitro (A) and in vitro (B): (A) RORγt mRNA levels in the kidney of USP25^−/− mice and wild mice at 14 days at the anti-GBM GN model; (B) CD4 T cells were isolated from the spleen of wild mice and USP25^−/− mice, and then induced to Th1, Th2 and Th17 cells. The mRNA levels of RORγt were measured after cell differentiation. Anti-GBM GN, anti-glomerular basement membrane glomerulonephritis; WT: wild type; bars represent means ± SEM; n = 3–4 each group; ^#p < 0.05; ^##p < 0.01.

Figure 5. USP25 increased after establishment of anti-GBM GN or Th17 cell differentiation. (A and B) The mRNA expression of USP25 in C57BL/6 mice with anti-GBM GN (A) and spontaneous lupus erythematosus mice (B) at different points in time. (C and D) Expression of USP25 after stimulating CD4+ T cells into Th17 cells in vitro. Anti-GBM GN: anti-glomerular basement membrane glomerulonephritis; Fas^lpr, a mouse model of spontaneous lupus erythematosus; MRL/MpJ is control mouse of Fas^lpr; bar, means ± SEM; ^#p < 0.05; ^##p < 0.01; ^###p < 0.001.

Data availability statement

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.