Immunomodulatory mechanism of interleukin-7 receptor α antibody attenuating renal injury in MRL/lpr lupus mice / 中华肾脏病杂志

ABSTRACT

Objective:To investigate the effect of interleukin (IL)-7 receptor α (IL-7Rα) antibody on the immune inflammation and renal injury in MRL/lpr lupus mice.Methods:Fifteen 3-4-week-old female MRL/lpr lupus mice (specific pathogen free) weighing 15-16 g were bred to 14-week-old and randomly divided into three groups: IL-7Rα antibody intervention group, isotype antibody (positive control) group and normal saline (negative control) group. The mice in the threc groups were intraperitoneally injected with IL-7Rα antibody, isotype antibody and normal saline respectively, with 100 μg three times a week for 4 weeks. At the age of 18-week old, the mice were sacrificed. Twenty-four-hour urinary protein was detected by Coomassie brilliant blue method, serum creatinine was detected by peroxidase method, and the expression of autoantibody (anti-double strand DNA antibody) and inflammatory factors such as tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and IL-21 was detected by enzyme-linked immunosorbent assay method. Renal pathology was detected by PAS and Sirius red staining, and CD3 and F4/80 in renal tissues were detected by immunohistochemistry method. Regulatory T cells, follicullar helper T cells (Tfh) and follicular regulatory T cells (Tfr) were detected by flow cytometry.Results:The 24-hour urinary protein, serum creatinine, serum anti-double strand DNA antibody and serum IFN-γ and IL-21 in the IL-7Rα antibody intervention group were significantly lower than those in the control groups (all P<0.01). However, there was no significant difference in serum TNF-α among the three groups ( F=0.39, P>0.05). The positive infiltrating cells of CD3 and F4/F80, and the ratio of type Ⅰ/Ⅲ collagen fibers ( F=41.11, P<0.01) of renal tissues in the IL-7Rα antibody intervention group were lower than those in the other two groups. Compared with the control groups, the ratio of regulatory T cells (CD4 +CD25 +Foxp3 +)/effector T cells (CD4 +CD25 +) in blood of IL-7Rα antibody intervention group increased ( F=21.64, P<0.01), while the ratio of Tfr (CD4 +CXCR5 +Foxp3 +)/Tfh (CD4 +CXCR5 +) in peripheral blood and spleen increased ( F=38.95, P<0.01; F=12.90, P<0.01). Conclusion:IL-7Rα antibody can reduce the production of autoantibodies such as anti-double strand DNA antibody and inflammatory factors by increasing the ratio of regulatory T cells and Tfr/Tfh, thus alleviating immune inflammation and renal damage in MRL/lpr lupus mice.