RESUMO
Systemic lupus erythematosus (SLE) is a multiple organ autoimmune disorder,including theliver,but the possible reason in impairment in the liver is still unclear.Our present study assessed alterations of transcription factor Foxp3+ regulatory T cells (Tregs) and several other immune molecules [programmed cell death 1 and its ligand (PD1 and PD-L1),and interleukin 10 (IL-10) and transform growth factor β (TGF-β)] in the liver and other major organs of lupus-prone BXSB mice by flow cytometry,real-time quantitative reverse trinscription PCR,and enzyme-linked immunosorbent assay.Results showed that both frequency and number of Foxp3+ Tregs were dramatically reduced in the thymus,spleen and kidney of the BXSB mice (P＜0.05),but those in the liver were kept in nearly normal range,when compared to negative control C57BL/6 mice.In comparison to control mice,the mRNA levels of Foxp3,PD1 and PD-L1 were significantly decreased in the kidneys of BXSB mice (P＜0.05),but there was no significant difference in the livers of the BXSB mice (P＞0.05).Protein levels of IL-10 and TGF-β in serum showed no significant difference between BXSB and C57BL/6 mice,but were significantly increased in the kidneys and livers of BXSB mice as compared with those in C57BL/6 mice (P＜0.05).These results suggest that reduced Foxp3+ Tregs are involved in the pathogenesis of SLE in BXSB mice,and relatively higher number of these cells in the livers than in the other target organs could constitute a protective mechanism against hepatic lesions in lupus-prone mice,which may provide insights into development of new therapeutic approaches in SLE patients.
RESUMO
Objective To explore the role of delivering programmed death (PD)-1 negative costimulation pathways in the prevention of murine BXSB lupus. Methods A recombinant adenovims containing the full-length mouse PD-L1 gene (AdPD-L1) was constructed and was introduced to the BXSB mice. The effect of immunoinhibitory receptor PD-1 on activated lymphocytes was investigated to evaluate its effect on prevention of lupus nephritis in BXSB mice. Results This intervention dramatically delayed the onset of proteinuria, effectively inhibited IgG autoantibody production, and significantly reduced hypercellularity and deposition of IgG in glomeruli, resulting in almost complete amelioration of lupus nephritis in these animals.Conclusion Our results suggest that simultaneous stimulation of PD-1-mediated pathway can potentially revent human lupus nephritis.
RESUMO
AIM: To investigate the effects of lupus recipe on immune system and lymphocyte subsets proliferation in splenic cells in BXSB mice. METHODS: Eighteen male BXSB mice model was used in the experiment. The model mice were divided into three groups: un-treated model group, lupus recipe (LR) treated group, and prednisone treated group. All model mice were killed in 10 weeks. The control group consisted of 6 syngeneic normal C57BL/6 male mice. The levels of total IgG and anti-dsDNA antibody in serum were detected by ELISA. The percentages of lymphocyte subsets (CD3+, CD4+, CD8+ T lymphocytes and CD19+, CD23+ B lymphocytes) were detected by using flow cytometry analysis. RESULTS: (1) The serum levels of total IgG and anti-dsDNA antibody in un-treated model group were higher than that in other groups. There was no differences among LR treated group, prednisone treated group and control group. (2) The percentages of CD3+, CD4+, CD8+ T lymphocytes and CD19+, CD23+ B lymphocytes in model group were obviously higher than that in normal control. (3) Compared to un-treated model group, the percentages of CD4+, CD8+ T lymphocytes and CD19+, CD23+ B lymphocytes in LR or prednisone treated group were significantly reduced, which closely reached the levels in normal group. CONCLUSIONS: The immune functions of T and B lymphocytes in BXSB mice are up-regulated. LR inhibits the activation of T and B lymphocytes, reduces the serum levels of IgG and auto-antibody production.