SBI enhanced MSC efficacy in treating R848-induced mice.
Our data showed that the efficacy of SBI was comparable to that of MSCs, as evidenced by the inhibition of spleen enlargement and the reduction of serum IgG, anti-dsDNA, urine protein levels, and kidney IgG and C3 deposition (Fig. 1). There was one mouse in the SBI plus MSCs treatment group died of cellular embolism during tail vein infusion of MSCs. Furthermore, the addition of SBI to MSCs treatment resulted in an enhanced the ability of MSCs to inhibit splenomegaly and serum ANA levels (Fig. 1B,D). Additionally, SBI increased the extent to which MSCs improved urine creatinine and serum urea nitrogen levels (Fig. 1G,H), suggesting a synergistic effect of SBI with MSCs in the treatment of R848-induced mice.
SBI synergized with MSCs to restore immune balance.
In order to examine the impact of SBI and MSCs on lymphocytes, the proportions of major T and B cell subsets was analyzed by flow cytometry (Fig. 2A-C). In comparison to mice treated with acetone, the percentages of T helper-1 (Th1) cells (CD4+INF-γ+), T helper-2 (Th2) cells (CD4+IL-4+), T helper-17 (Th17) cells (CD4+IL-17+), Tfh cells (CD4+CXCR5+PD-1+), germinal center (GC) B cells (B220+CD95+GL7+) and plasmablast (B220+CD138-) in the splenocytes of R848-induced mice exhibited an increase, while the proportions of Treg cells (CD4+CD25+Foxp3+) and memory B cells (B220+IgD+CD38+) demonstrated a decrease. The administration of SBI resulted in a significant reduction in the proportion of Tfh cells and an increase in the proportion of Treg cells. Consequently, the percentage of plasmablast cells in splenocytes of mice induced with R848 was also decreased following SBI treatment (Fig. 2D). Compared to MSCs, combined treatment with SBI lowed the percentages of Th1 and Th2 cells, decreased the percentage of Tfh cells (Fig. 2), and further improved the imbalance of Tfh/Treg cells (Fig. 2). Meanwhile, the absolute number of Tfh cells was significantly decreased after SBI plus MSCs treatment (Fig. S1), supporting that SBI could act synergistically with MSCs to rebalance the immune system.