| Objective: Systemic lupus erythematosus(SLE)is an autoimmune disease caused by autoimmune dysfunction.It is characterized by severe and persistent inflammation that causes tissue damage to multiple organs,especially lupus nephritis(LN).Though it is thought that LN is mainly caused by the deposition of immune complexes consists of complements and antibodies,the specific mechanism is still unknown.Our previous study has found that the level of Interleukin-22(IL-22)in serum and kidney was increased in patients with LN.Therefore,we used the MRL/lpr lupus-prone mice model to explore the role of IL-22 in the pathogenesis of lupus nephritis and its mechanism.Methods: Blood,urine and kidneys of MRL/lpr lupus mice at different ages were collected.Enzyme linked immunosorbent assay(ELISA),real-time quantitative polymerase chain reaction(RT-q PCR)and immunohistochemistry were used to detect the level of IL-22 in serum or kidney.MRL/lpr mice were injected with anti-IL-22 monoclonal antibody,isotype antibody,prednisone or saline in groups.IL-22 knockout MRL/lpr mice were generated.Renal tubular epithelial cells were stimulated with recombinant IL-22,and western blot was used to detect the signaling pathway activated by IL-22.Results: In serum of MRL/lpr mice at different ages,as the age increased,lupus nephritis worsened,and the level of IL-22 increased significantly.And the level of IL-22 in kidney also increased with age.Anti-IL-22 monoclonal antibody-treated lupus mice had significantly alleviated renal lesions and improved renal function.Compared with MRL/lpr mice,the survival rate of IL-22 gene knockout lupus mice was improved,and systemic disease performance and lupus nephritis were alleviated.Significant phosphorylation activation of the STAT3 signaling pathway can be detected when recombinant IL-22 was added to the renal tubular epithelial cells in vitro.Conclusions: IL-22 may play a pathogenic role in lupus nephritis,and may be a potential therapeutic target for lupus nephritis. |
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