Haijun Ma, China
The First Affiliated Hospital Of Xinxiang Medical University Department of Rheumatology and ImmunologyPresenter of 1 Presentation
MESENCHYMAL STEM CELLS REGULATE THE ACTIVATED COMPLEMENT C5 BY CLUSTERIN IN THE TREATMENT OF LUPUS NEPHRITIS
Abstract
Background and Aims
The excessive complement activation participated in the development of lupus nephritis (LN). Mesenchymal stem cells (MSCs) exhibit clinical efficacy for severe LN, however, it remains unknown whether MSCs could regulate complement activation. The present study aimed to investigate the dysregulaiton of the complement in LN, examine the effect of MSCs on lupus mice, and explore the possibility of MSCs regulating complement activation as well as the related mechanisms.
Methods
Levels of C5a, C5b-9, and clusterin (CLU) were detected in plasma and renal biopsy specimens. The effect of MSCs and cyclophosphamide was explored on B6.lpr mice. Levels of anti-dsDNA Ab, C3, C5a, C5b-9, and CLU were detected in mice. Histopathological evaluation was performed in renal tissues. Expressions of CLU were detected in MSCs stimulated by interferon-α (IFN-α). MSCs-derived CLU was purified and its functional characteristic was also identified.
Results
Significantly elevated activated complement C5 and decreased CLU were found in LN patients, which were correlated with proteinuria and pathological index. Compared to control mice, the proteinuria, proliferative glomerulonephritis, and depositions of IgG, C3 as well as C5b-9 were significantly reduced in MSCs-treated mice. Meanwhile, plasma C3 and CLU were significantly increased in these mice. Mechanistically, MSCs basally expressed CLU, and IFN-α stimulation promoted MSCs secreting CLU in vitro. Importantly, MSCs-derived CLU effectively inhibited complement C9 polymerization.
Conclusions
Dysregulaiton of complement of C5 was involved in the pathogenesis of LN. Allogeneic MSCs effectively improved the glomerulonephritis in lupus mice by limiting the effect of activated C5 via clusterin, which would be a novel therapeutic target for LN.