Related Experiment Video
Updated: May 10, 2026
Murine Model of CD40-activation of B cells
Published on: March 5, 2010
CD40 gene silencing reduces the progression of experimental lupus nephritis modulating local milieu and systemic
Èlia Ripoll1, Ana Merino, Immaculada Herrero-Fresneda
1Laboratory of Experimental Nephrology, IDIBELL.Hospital Universitari de Bellvitge, L'Hospitalet, Barcelona, Spain.
Abstract:
Lupus nephritis (LN) is an autoimmune disorder in which co-stimulatory signals have been involved. Here we tested a cholesterol-conjugated-anti-CD40-siRNA in dendritic cells (DC) in vitro and in a model of LPS to check its potency and tissue distribution. Then, we report the effects of Chol-siRNA in an experimental model of mice with established lupus nephritis. Our in vitro studies in DC show a 100% intracellular delivery of Chol-siRNA, with a significant reduction in CD40 after LPS stimuli. In vivo in ICR mice, the CD40-mRNA suppressive effects of our Chol-siRNA on renal tissue were remarkably sustained over a 5 days after a single preliminary dose of Chol-siRNA. The intra-peritoneal administration of Chol-siRNA to NZB/WF1 mice resulted in a reduction of anti-DNA antibody titers, and histopathological renal scores as compared to untreated animals. The higher dose of Chol-siRNA prevented the progression of proteinuria as effectively as cyclophosphamide, whereas the lower dose was as effective as CTLA4. Chol-siRNA markedly reduced insterstitial CD3+ and plasma cell infiltrates as well as glomerular deposits of IgG and C3. Circulating soluble CD40 and activated splenic lymphocyte subsets were also strikingly reduced by Chol-siRNA. Our data show the potency of our compound for the therapeutic use of anti-CD40-siRNA in human LN and other autoimmune disorders.
Insights
Cholesterol-conjugated-anti-CD40-siRNA effectively targets CD40 in dendritic cells and renal tissue, showing promise for lupus nephritis treatment. This compound reduced autoantibodies and kidney damage in mouse models.
Area of Science:
- Immunology
- Nephrology
- Pharmacology
Background:
- Lupus nephritis (LN) involves autoimmune responses and co-stimulatory signals.
- Targeting CD40 is a potential therapeutic strategy for autoimmune disorders.
Purpose of the Study:
- To evaluate the efficacy and tissue distribution of cholesterol-conjugated-anti-CD40-siRNA (Chol-siRNA).
- To assess Chol-siRNA's therapeutic potential in a mouse model of lupus nephritis.
Main Methods:
- In vitro studies using dendritic cells (DCs) and LPS stimulation.
- In vivo studies in ICR and NZB/WF1 mice models.
- Assessment of CD40 mRNA, autoantibody titers, proteinuria, renal histopathology, and immune cell infiltration.
Main Results:
- Chol-siRNA demonstrated 100% intracellular delivery in DCs and sustained CD40 mRNA suppression in renal tissue.
- Treatment reduced anti-DNA antibody titers, proteinuria, and kidney damage markers.
- Chol-siRNA effectively decreased immune cell infiltrates and immune deposits in kidneys.
Conclusions:
- Chol-siRNA is a potent therapeutic agent for lupus nephritis.
- The compound shows promise for treating human LN and other autoimmune diseases.
