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.