Abstract
BackgroundGraft-versus-host disease (GvHD) is a critical complication after allogeneic hematopoietic stem cell transplantation (HSCT). The immunosuppressants given to patients undergoing allogeneic HSCT disturb the microbiome and the host immune system, potentially leading to dysbiosis and inflammation, and may affect immune function and bone marrow transplantation. The intestinal microbiome is a target for the development of novel therapies for GvHD. Lactobacillus species are widely used supplements to induce production of antimicrobial and anti-inflammatory factors.MethodsWe determined the effect of the combination of Lactobacillus acidophilus and FK506 on GvHD following major histocompatibility complex-mismatched bone marrow transplantation.ResultsThe combination treatment suppressed IFN-γ and IL-17-producing T cell differentiation, but increased Foxp3+Treg differentiation and IL-10 production. Also, the combination treatment and combination treated-induced Treg cells modulated the proliferation of murine alloreactive T cells in vitro. Additionally, the combination treatment upregulated Treg-related genes—Nt5e, Foxp3, Ikzf2, Nrp1 and Itgb8—in murine CD4+-T cells. The combination treatment also alleviated GvHD clinically and histopathologically by controlling the effector T cell and Treg balance in vivo. Moreover, the combination treatment decreased Th17 differentiation significantly and significantly upregulated Foxp3 and IL-10 expression in peripheral blood mononuclear cells from healthy controls and liver transplantation (LT) patients.ConclusionsTherefore, the combination of L. acidophilus and FK506 is effective and safe for patients undergoing allogeneic hematopoietic stem cell transplantation.
Highlights
Graft-versus-host disease (GvHD) is a critical complication after allogeneic hematopoietic stem cell transplantation (HSCT)
Combination treatment modulates murine T‐cell proliferation in vitro First, we investigated the effect of the combination treatment on murine IFN-γ-producing T cell, IL-17-producing T cell, and Treg cell differentiation in vitro
The combination treatment was significantly decreased CD8+ type 1 cytotoxic T cell (Tc1) and IL-17-producing CD8+ (Tc17) cell proliferation, and a single treatment with L. acidophilus was more effective than FK506 single on Tc 1 cells (Fig. 1c)
Summary
Graft-versus-host disease (GvHD) is a critical complication after allogeneic hematopoietic stem cell transplantation (HSCT). The immunosuppressants given to patients undergoing allogeneic HSCT disturb the microbi‐ ome and the host immune system, potentially leading to dysbiosis and inflammation, and may affect immune func‐ tion and bone marrow transplantation. Lactobacillus species are widely used supplements to induce production of antimicrobial and anti-inflam‐ matory factors. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a remedial treatment modality for most hematologic malignancies. Graft-versus-host disease (GvHD) affects the skin, liver, and gastrointestinal tract. T cells in the graft and leads to a high rate of transplantation-related mortality [1, 2]. Tacrolimus ( known as FK506), a calcineurin inhibitor, is an anti-T-cell agent that is among the most widely used immunosuppressants [3]. The use of FK506 is associated with nephrotoxicity and can lead to dysbiosis [8,9,10]
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