Abstract
BackgroundSilibinin has been shown to have anti-HCV activity and immune-modulating properties by regulating dendritic cell (DC) function. DCs are antigen-presenting cells that, together with regulatory T cells (Treg), play a pivotal role in controlling alloimmune, as well as anti-HCV immune responses.MethodsTwelve liver transplant patients with HCV recurrence received iv infusion of Silibinin (iv-SIL) for 14 consecutive days. Using flow cytometry, before and at the end of treatment, we determined the frequencies of circulating myeloid (m) and plasmacytoid (p) DC and Treg and the expression of costimulatory/coregulatory molecules by the DC subsets and Treg. Statistical analysis was performed using the paired Student’s t test and Pearson correlation test.ResultsAfter iv-SIL treatment, we observed an elevated plasmacytoid dendritic cell (pDC)/myeloid dendritic cell (mDC) ratio, while pDC displayed lower HLA-DR and higher immunoglobulin-like transcript 4 (ILT4), CD39, and HLA-G expression compared to the pretreatment baseline. In addition, after iv-SIL, mDC showed increased inducible costimulator ligand (ICOSL) expression. No changes were detected in Treg frequency or programed death (PD)-1 expression by these cells. Moreover, several correlations between DC/Treg markers and clinical parameters were detected.ConclusionsThis descriptive study, in liver transplant patients with HCV recurrence, reveals the impact of iv-SIL on DC and Treg. The changes observed in circulating pDC and mDC that have previously been associated with tolerogenic conditions shed new light on how iv-SIL may regulate anti-viral and alloimmunity. We have also observed multiple clinical correlations that could improve the clinical management of liver transplant patients and that deserve further analysis.
Highlights
Silibinin has been shown to have anti-HCV activity and immune-modulating properties by regulating dendritic cell (DC) function
Our findings reveal changes in circulating plasmacytoid dendritic cell (pDC) and myeloid dendritic cells (mDC) that have previously been associated with tolerogenic conditions suggesting how iv infusion of Silibinin (iv-SIL) might regulate anti-viral and alloimmunity
We have observed multiple clinical correlations that could improve the clinical management of liver transplant patients and that deserve further analysis
Summary
Silibinin has been shown to have anti-HCV activity and immune-modulating properties by regulating dendritic cell (DC) function. In vivo and in vitro studies have shown that the anti-HCV effect of Silibinin involves stimulation of toll-like receptor (TLR) 7, interferon regulatory factor 3, and p38 mitogenactivated protein kinase pathways [1]. The safety and efficacy of Silibinin as anti-viral therapy has been demonstrated in chronic HCV-infected patients and in liver transplant patients with HCV recurrence unresponsive to standard combined therapy with interferon/ribavirin [2]. There is evidence that Silibinin has immunemodulating properties and polarizes Th1/Th2 immune responses through functional modifications of dendritic cells (DCs) [3]. DCs are innate immune cells that are Castellaneta et al Transplantation Research (2016) 5:1 important in the induction and regulation of adaptive immunity. Several subsets of DC have been identified, principally conventional myeloid (m) DC and type-1 interferon (IFN)-producing plasmacytoid (p) DC, that may be specialized for modifying the quality, strength, and duration of immune responses [4, 5]
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