Reducing progression of experimental lupus nephritis via inhibition of the B7/CD28 signaling pathway
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Updated: Apr 9, 2026
The bm12 Inducible Model of Systemic Lupus Erythematosus SLE in C57BL/6 Mice
Published on: November 1, 2015
Li Huang1, Yong Kong2, Jing Wang3
1Department of Internal Medicine, Children's Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China.
Abstract:
The aim of the present study was to evaluate the effects of the B7/cluster of differentiation (CD)28 signaling pathway on experimental lupus nephritis and examine the molecular mechanism involved by inhibiting the B7/CD28 signaling pathway. A lupus nephritis model in C57BL/6 J mice was induced via intraperitoneal injection of pristane. A recombinant B7‑1 short hairpin RNA (shRNA) lentivirus vector was constructed by synthesis and splicing. A neutralizing mouse anti‑human B7‑1 antibody termed 4E5 was also prepared. The mouse model of lupus nephritis was treated with B7‑1 shRNA and 4E5 via injection through the tail vein. The silencing effects of B7‑1 shRNA lentiviral infection on target molecules were evaluated using immunofluorescence and flow cytometry. The levels of protein in the urine were detected using Albustix test paper each month over 10 months. The concentration of interleukin (IL)‑4 and interferon‑γ in the serum was determined using an ELISA. The immune complex (IC) deposits in the kidney were analyzed using direct immunofluorescence. The results demonstrated that the C57BL/6 J mouse lupus nephritis model was successfully constructed with immune cells activated in the spleen of the mice, increases in the concentration of anti‑nuclear antibody (ANA) and anti‑double stranded DNA antibodies as well as positive IC formation. Following B7‑1 shRNA lentivirus or 4E5 treatment, CD11b+B7‑1+, CD11c+B7‑1+ and CD21+B7‑1+ cells in the spleen of the mice were significantly reduced. The concentration of ANA and IL‑4 in the serum was also decreased. The concentration of urine protein was reduced and it was at its lowest level in the 4E5 early intervention group. It was also revealed that the immunofluorescence intensity of the IC deposits was weak in the 4E5 early intervention group. In conclusion, inhibiting the B7‑1/CD28 signaling pathway is able to alleviate experimental lupus nephritis and provides an experimental basis for the therapeutic use of blocking the B7‑1/CD28 signaling pathway in human lupus nephritis and other autoimmune disorders.
Insights
Inhibiting the B7/cluster of differentiation (CD)28 signaling pathway effectively reduced lupus nephritis in mice. This approach offers a potential therapeutic strategy for lupus nephritis and other autoimmune diseases.
Area of Science:
- Immunology
- Nephrology
- Molecular Biology
Background:
- Experimental lupus nephritis is a complex autoimmune disease characterized by immune complex deposition and inflammation.
- The B7/cluster of differentiation (CD)28 signaling pathway plays a crucial role in immune cell activation and autoimmune responses.
- Targeting this pathway presents a potential therapeutic strategy for autoimmune disorders like lupus nephritis.
Purpose of the Study:
- To evaluate the therapeutic effects of inhibiting the B7/CD28 signaling pathway on experimental lupus nephritis.
- To investigate the underlying molecular mechanisms by which B7/CD28 pathway inhibition impacts lupus nephritis.
Main Methods:
- A lupus nephritis mouse model was induced using pristane.
- Inhibition of the B7/CD28 pathway was achieved using B7-1 short hairpin RNA (shRNA) lentivirus and a neutralizing anti-B7-1 antibody (4E5).
- Effects were assessed via immunofluorescence, flow cytometry, urine protein analysis, ELISA for cytokine levels, and kidney immune complex analysis.
Main Results:
- Successful induction of the lupus nephritis model was confirmed by immune cell activation, autoantibodies, and immune complex formation.
- Treatment with B7-1 shRNA or 4E5 significantly reduced specific immune cell populations (CD11b+B7-1+, CD11c+B7-1+, CD21+B7-1+) in the spleen.
- Therapeutic interventions decreased anti-nuclear antibody (ANA) and interleukin-4 (IL-4) levels, reduced urine protein, and weakened kidney immune complex deposits, particularly with early 4E5 intervention.
Conclusions:
- Inhibition of the B7-1/CD28 signaling pathway demonstrates significant therapeutic potential in alleviating experimental lupus nephritis.
- This study provides an experimental foundation for exploring B7-1/CD28 pathway blockade as a treatment for human lupus nephritis and other autoimmune diseases.
