Systemic Lupus Erythematosus (SLE) is an autoimmune disease that affects multiple organs simultaneously. The immune system generates antibodies against intracellular antigens, leading to the formation of immune complexes (ICs) in the blood. These ICs then accumulate at specific anatomical sites, triggering a cascade reaction that results in the degradation not only of the ICs themselves but also of the surrounding tissues (e.g., kidneys, spleen, lungs, cartilage).
Gelatinase B/matrix metalloproteinase-9 (MMP-9) inhibitors are a controversial treatment for SLE, as published results to date have been inconsistent. Some cases have also shown that treatment with MMP-9 inhibitors may induce SLE.
By homogenizing liver and spleen samples using the Precellys 24 in various genetically induced and non-induced SLE mouse models, researchers demonstrated that the presence of MMP-9 in organs such as the liver and spleen is associated with a reduced risk of inflammation and, consequently, a reduction in the pathological effects of the disease.
This discovery enabled the team to conduct additional experiments, which provided evidence that MMP-9 plays an essential role in both the prevention and the clearance of immune complexes.
Figure 1: Determination of C3d concentration by ELISA in the spleen (C) and kidney (D).
WT = Wild type
MMP-9 -/- = MMP-9 knockout model
LPR -/- = SLE model (FAS apoptosis pathway knockout)
C3d = A complement fragment that binds to immune complexes and facilitates their phagocytosis by immune cells.
The absence of a significant difference in C3d levels in the kidneys and spleen of MMP-9 -/- mice, and the significant increase in C3d in these same organs in LPR -/-/MMP-9 -/- mice compared to controls, demonstrate that the presence of MMP-9 reduces the formation or persistence of immune complexes in these organs.
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Precellys enabled fast, efficient, and standardized homogenization of fragile tissues, preserving molecular integrity and ensuring high reproducibility, essential conditions for studying delicate inflammatory pathways in autoimmune models.
Read the full article to explore how Precellys® contributed to uncovering the unexpected role of MMP-9 in lupus and what it could mean for future treatment strategies.
